Dynamics and optimal control of a spatial diffusion HIV/AIDS model with ART and PrEP treatments

In this paper, to investigate the synthetic effect of PrEP (pre-exposure prophylaxis) and ART (antiretrovial therapy) on HIV transmission among MSM (men who have sex with men) in heterogenous environment, an realistic HIV epidemic model with spatial diffusion is established. Here, HIV infectious people are divided into three immunity based compartments, i.e., CD4+ T cell count less than 350, between 350 and 500, and more than 500, respectively. The basic reproduction number $R_0$ is established and proved as a threshold parameter: The global asymptotic stability of the disease-free steady state holds for $R_0<1$, and the disease will be present if $R_0>1$. Considering the substantial advantages of PrEP and ART in controlling HIV transmissions among MSM, the optimal control problem is presented for the case of positive constant diffusion coefficients, which minimize the total population of susceptible individual and HIV infected individual, the cost of PrEP and ART thearpy. As an illustration of our theoretical results, we conduct numerical simulations. We also conduct an optimal control case study where model parameters are estimated from the demographic and epidemiological data from China. This work suggests: (1) Spatial factors cannot be ignored during the HIV intervention; (2)Taking the PrEP intervention measure for HIV transmissions among MSM as early as possible will help to improve the control efficiency and reduces its cost; (3) Reducing the PrEP drug costs will promote the efficiency of PrEP treatment in preventing the spread of HIV among MSM.

Maasai Girls’ Experiences of Ukimwi ni Homa (AIDS Is a Fever): Idioms of Vulnerability and HIV Risk in East Africa

There have been enormous strides in response to the AIDS epidemic in the past decades; however, adolescent girls and young women (AGYW) remain at high risk for new HIV infection throughout sub-Saharan Africa. Recognizing this continued discrepancy, I call for more attention to girls’ perceptions of vulnerabilities by revisiting an ethnographic study of HIV risk carried out in 2004 in a rural community in Kenya. My analysis situates Maasai AGYW perceptions and understandings of HIV risk as a culturally constructed idiom of distress: “Ukimwi ni Homa” (AIDS is a fever). I examine the emic perspectives of HIV vulnerability and the association of sexual relationships within the context of economic precarity. Findings demonstrate how references to fevers expressed feelings of helplessness, which increased indifference to HIV risk. This indifference led AGYW to prioritize imminent economic needs over long-term effects of a viral infection that they perceived as inevitable. Critically reflecting on AGYW understandings of their own risk perceptions can influence effective HIV intervention design. My conclusions support the need for tailoring combination prevention approaches to address perceived vulnerabilities within populations. Such perspectives add valuable insights to studies rooted in cultural constructions of illness perspective.

Medroxyprogesterone Acetate (MPA) Enhances HIV-1 Accumulation and Release in Primary Cervical Epithelial Cells by Inhibiting Lysosomal Activity

Medroxyprogesterone acetate (MPA) is one of the most widely used contraceptives in the world. Epidemiologic studies have uncovered a possible link between the use of MPA and an increased risk of HIV-1 transmission. However, the understanding of the mechanism is still limited. Our previous publication demonstrated that the lysosomal activity in human vaginal epithelial cells attenuated the trafficking of viral particles during HIV-1 transcytosis. In this study, we show that treating human primary cervical epithelial cells with MPA led to a reduction in lysosomal activity. This reduction caused an increase in the intracellular HIV-1 accumulation and, consequently, an increase in viral release. Our study uncovers a novel mechanism by which MPA enhances HIV-1 release in primary cervical epithelial cells, thus providing vital information for HIV intervention and prevention.

Ending the HIV epidemic using National HIV Behavioral Surveillance (NHBS): Recommendations based on DC model

Introduction Social network strategies have been used by health departments to identify undiagnosed cases of HIV. Heterosexual cycle (HET4) of National HIV Behavioral Surveillance (NHBS) is a social network strategy implemented in jurisdictions. The main objectives of this research are to 1) evaluate the utility of the NHBS HET cycle data for network analysis; 2) to apply statistical analysis in support of previous HIV research, as well as to develop new research results focused on demographic variables and prevention/intervention with respect to heterosexual HIV risk; and 3) to employ NHBS data to inform policy with respect to the EHE plan. Method We used data from the 2016 NHBS HET4 (DC). A total of 747 surveys were collected. We used the free social-network analysis package, GEPHI, for all network visualization using adjacency matrix representation. We additionally conducted logistic regression analysis to examine the association of selected variables with HIV status in three models representing 1) demographic and economic effects, 2) behavioral effects, and 3) prevention-intervention effects. Results The results showed 3% were tested positive. Seed 1 initiated the largest networks with 426 nodes (15 positives); seed 4 with 273 nodes (6 positives). Seed 3 had 35 nodes (2 positives). All 23 HIV diagnoses were recruited from 4 zip-codes across DC. The risk of testing positive was higher among people high-school dropouts (Relative Risk (RR) (25.645); 95 CI% 5.699, 115.987), unemployed ((4.267); 1.295, 14.064), returning citizens ((14.319); 4.593, 44.645). We also found in the final model higher association of pre-exposure prophylaxis (PrEP) awareness among those tested negative ((4.783); 1.042, 21.944) and HIV intervention in the past 12 months with those tested positive ((17.887); 2.350,136.135). Conclusion The network visualization was used to address the primary aim of the analysis-evaluate the success of the implementation of the NHBS as a social network strategy to find new diagnoses. NHBS remains one of the strongest behavioral supplements for DC’s HIV planning activities. As part of the evaluation process our analysis helps to understand the impact of demographic, behavioral, and prevention efforts on peoples’ HIV status. We strongly recommend other jurisdictions use network visualizations to evaluate the efficacy in reaching hidden populations.

Deep–sequence phylogenetics to quantify patterns of HIV transmission in the context of a universal testing and treatment trial — BCPP/ Ya Tsie trial

Mathematical models predict that community–wide access to HIV testing–and–treatment can rapidly and substantially reduce new HIV infections. Yet several large universal test–and–treat HIV prevention trials in high–prevalence epidemics demonstrated variable reduction in population–level incidence. To elucidate patterns of HIV spread in universal test–and–treat trials we quantified the contribution of geographic–location, gender, age and randomized–HIV–intervention to HIV transmissions in the 30–community Ya Tsie trial in Botswana (estimated trial population: 175,664). Deep–sequence phylogenetic analysis revealed that most inferred HIV transmissions within the trial occurred within the same or between neighboring communities, and between similarly–aged partners. Transmissions into intervention communities from control communities were more common than the reverse post–baseline (30% [12.2 – 56.7] versus 3% [0.1 – 27.3]) than at baseline (7% [1.5 – 25.3] versus 5% [0.9 – 22.9]) compatible with a benefit from treatment–as–prevention. Our findings suggest that population mobility patterns are fundamental to HIV transmission dynamics and to the impact of HIV control strategies.

IMPAACT 2016: Operationalizing HIV Intervention Adaptations to Inform the Science and Outcomes of Implementation

Introduction: Uptake of evidence-based interventions for adolescents and young adults living with HIV (AYA-LWH) in sub-Saharan Africa (SSA) is complex, and cultural differences necessitate local adaptations to enhance effective implementation. Few models exist to guide intervention tailoring, yet operationalizing strategies is critical to inform science and implementation outcomes, namely acceptability, appropriateness, feasibility, fidelity, and sustainability. This paper describes operationalizing the ADAPT-ITT framework applied to a manualized trauma-informed cognitive behavioral therapy (TI-CBT) intervention addressing mental and sexual health for AYA-LWH in SSA in preparation for a randomized controlled trial (RCT).Methods: Phase 1 of the RCT focused on operationalizing ADAPT-ITT steps 3–7 to tailor the intervention for use in eight sites across Botswana, Malawi, South Africa, and Zimbabwe. Well-defined processes were developed to supplement the general guidelines for each step to provide clear, consistent direction on how to prepare and conduct each step, including documenting, assessing, and determining adaptations, while maintaining intervention fidelity. The processes provided efficient standardized step-by-step progression designed for future replication. All sites participated in Phase 1 using the created tools and strategies to translate and present the TI-CBT to community stakeholders for feedback informing local adaptations.Results: The research team developed and operationalized materials guiding adaptation. A translation review process verified local adaptability, maintained core concepts, and revealed differing interpretations of words, idioms, and culturally acceptable activities. Strategically designed tools comprised of feedback and translation verification forms resulted in meticulous management of adaptations. Robust collaborations between investigators, research managers, site personnel, and topical experts maximized multidisciplinary expertise, resulting in ~10–15 personnel per site facilitating, collecting, assessing, and integrating local feedback. Processes and tools operationalized in steps 3–7 effectively addressed implementation outcomes during community engagements (n = 108), focus groups (n = 5–8 AYA-LWH and caregivers per group), and strategic training of youth leaders.Discussion: This paper offers a novel generalizable approach using well-defined processes to guide intervention adaptation building on the ADAPT-ITT framework. The processes strengthen the science of implementation and provide much-needed specificity in adaptation steps to optimize and sustain real-world impact and help researchers and community stakeholders maximize existing infrastructure, culture, and resources to inform implementation strategies.

Primary care oncology model (PCOM): Implementation of a model integrating primary and oncology care for patients taking oral anticancer agents.

TPS1587 Background: Non-adherence to oral anticancer agents (OAA) has been reported among 30% of individuals. Often, individuals with cancer are not just managing their new OAA but also medications to treat multiple chronic conditions (MCC). Multiple factors contribute to the extent patients on OAAs and MCC medications adhere to therapy. The objective of this study is to improve medication, symptom, and disease management of patients with hematological malignancies and MCC through care coordination between pharmacists. Methods: Design. This is a multi-center prospective single arm pilot study at two academic medical centers in Michigan and Tennessee. Subjects. Ninety participants will be recruited, 60 from site 1 and 30 from site 2. Inclusion criteria are: adults > 18 years, diagnosed with and initiating oral treatment for chronic myeloid leukemia, chronic lymphocytic leukemia, or multiple myeloma, diagnoses of at least 2 chronic conditions, where one is type 2 diabetes, hypertension, congestive heart failure, depression/anxiety, gastroesophageal reflux disease, hyperlipidemia, or chronic obstructive pulmonary disease, taking at least two chronic medications, and able to provide electronic consent. Exclusion criteria are: inability to speak English, and diagnosis of type 1 diabetes or HIV. Intervention. Participants will complete two Patient Reported Outcome Measures (PROMs) for their OAA that will be reviewed by the oncology pharmacist, with follow-up to the care team if needed. Participants will be scheduled for a Comprehensive Medication Review with a primary care pharmacist for up to two visits for their chronic medications. The intervention over 2 months, and the oncology and primary care pharmacists communicate via electronic health record about medications, symptoms, and disease control. Outcomes. The primary endpoints are (a) dose-adjusted adherence by proportion days covered (PDC) for the OAA and (b) PDC for chronic condition medications, assessed using 6 months of prescription claims. Data will be collected from patients using REDCap surveys and abstracted data will be entered into REDCap. Implementation by pharmacists and patient acceptability will be examined. Analysis. The association of OAA and chronic medication adherence (PDC) will be examined via correlation. Participant demographics,clinical characteristics, and the symptom experience from the PROM will be described. Using CMR results, medication problems, recommendations, and changes will be provided. Program implementation will be assessed and patient perceptions obtained from post-CMR interviews. A joint display for the quantitative and qualitative data for feasibility, appropriateness, and acceptability from pharmacists will be completed. Results: Screening and recruitment has begun. Clinical trial information: NCT04595851 and NCT04663100.

Outcomes of Implementing in the Real World the Women's Health CoOp Intervention in Cape Town, South Africa

Women in South Africa living with HIV who use alcohol may not adhere to ART, affecting the country’s 90-90-90 targets. The Women’s Health CoOp (WHC), a woman-focused HIV intervention, has shown efficacy in numerous trials with key populations of women in South Africa who use alcohol and drugs. In a hybrid implementation effectiveness study, the WHC was implemented in usual care clinics by healthcare providers in a modified stepped-wedge design. We present the outcomes of alcohol use and ART adherence with 480 women, with a 95% 6-month follow-up rate across 4 implementation cycles. Compared with the first cycle, women in the fourth cycle were significantly less likely (OR = 0.10 [95% CI 0.04, 0.24]) to report alcohol use disorder risk and were 4 times more likely (OR = 4.16 [95% CI 1.05, 16.51]) to report ART adherence at 6-month follow-up. Overall, acceptability and satisfaction were extremely high. The WHC intervention was successful in reaching key populations of women to reduce alcohol use and increase ART adherence, which is essential for South Africa to reach the 90-90-90 goals.