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

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

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

Building capacity in implementation science research training at the University of Nairobi.

BACKGROUND: Health care systems in sub-Saharan Africa, and globally, grapple with the problem of closing the gap between evidence-based health interventions and actual practice in health service settings. It is essential for health care systems, especially in low-resource settings, to increase capacity to implement evidence-based practices, by training professionals in implementation science. With support from the Medical Education Partnership Initiative, the University of Nairobi has developed a training program to build local capacity for implementation science. METHODS: This paper describes how the University of Nairobi leveraged resources from the Medical Education Partnership to develop an institutional program that provides training and mentoring in implementation science, builds relationships between researchers and implementers, and identifies local research priorities for implementation science. RESULTS: The curriculum content includes core material in implementation science theory, methods, and experiences. The program adopts a team mentoring and supervision approach, in which fellows are matched with mentors at the University of Nairobi and partnering institutions: University of Washington, Seattle, and University of Maryland, Baltimore. A survey of program participants showed a high degree satisfaction with most aspects of the program, including the content, duration, and attachment sites. A key strength of the fellowship program is the partnership approach, which leverages innovative use of information technology to offer diverse perspectives, and a team model for mentorship and supervision. CONCLUSIONS: As health care systems and training institutions seek new approaches to increase capacity in implementation science, the University of Nairobi Implementation Science Fellowship program can be a model for health educators and administrators who wish to develop their program and curricula

The role of G protein gene GNB3 C825T Polymorphism in HIV-1 acquisition, progression and immune activation

<p>Abstract</p> <p>Background</p> <p>The <it>GNB3 C825T </it>polymorphism is associated with increased G protein-mediated signal transduction, SDF-1α-mediated lymphocyte chemotaxis, accelerated HIV-1 progression, and altered responses to antiretroviral therapy among Caucasian subjects. The <it>GNB3 </it>825T allele is highly prevalent in African populations, and as such any impact on HIV-1 acquisition or progression rates could have a dramatic impact. This study examines the association of the 825T polymorphism with HIV-1 acquisition, disease progression and immune activation in two African cohorts. <it>GNB3 </it>825 genotyping was performed for enrolees in both a commercial sex worker cohort and a perinatal HIV transmission (PHT) cohort in Nairobi, Kenya. <it>Ex vivo </it>immune activation was quantified by flow cytometry, and plasma chemokine levels were assessed by cytokine bead array.</p> <p>Results</p> <p><it>GNB3 </it>genotype was not associated with sexual or vertical HIV-1 acquisition within these cohorts. Within the Pumwani cohort, <it>GNB3 </it>genotype did not affect HIV-1 disease progression among seroconverters or among HIV-1-positive individuals after adjustment for baseline CD4 count. Maternal CD4 decline and viral load increase in the PHT cohort did not differ between genotypes. Multi-parametric flow cytometry assessment of T cell activation (CD69, HLA-DR, CD38) and Treg frequency (CD25⁺FOXP3⁺) found no differences between genotype groups. Plasma SDF-1α, MIP-1β and TRAIL levels quantified by cytokine bead array were also similar between groups.</p> <p>Conclusions</p> <p>In contrast to previous reports, we were unable to provide evidence to suggest that the <it>GNB3 C825T </it>polymorphism affects HIV-1 acquisition or disease progression within African populations. <it>Ex vivo </it>immune activation and plasma chemokine levels were similarly unaffected by <it>GNB3 </it>genotype in both HIV-1-negative and HIV-1-positive individuals. The paucity of studies investigating the impact of <it>GNB3 </it>polymorphism among African populations and the lack of mechanistic studies make it difficult to assess the true biological significance of this polymorphism in HIV-1 infection.</p