Attaining 95-95-95 through Implementation Science: 15 Years of Insights and Best Practices from the Walter Reed Army Institute of Research’s Implementation of the U.S. President’s Emergency Plan for AIDS Relief

Lee, Elizabeth H; Ganesan, Kavitha; Khamadi, Samoel; Meribe, S C; Njeru, Dorothy; Adamu, Yakubu; Magala, Fred; Crowell, Trevor A; Akom, Eniko; Agaba, Patricia A; Desai, Priyanka; Hamm, Tiffany E.; Teyhen, Deydre S.; Ake, Julie A; Polyak, Christina S.; Shaffer, Douglas; Sawe, Fredrick; Hickey, Patrick W.

doi:10.4269/ajtmh.20-0541

Cited by 2 publications

(1 citation statement)

References 40 publications

(39 reference statements)

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“…The high burden of preventable infectious diseases in resource-constrained countries, particularly in sub-Saharan Africa (SSA), and the recent rise in non-communicable diseases [1] has led to an increase in research studies and clinical trials conducted in these regions [2][3][4]. Clinical laboratory RIs are necessary for screening potential study participants, assessing adverse events, monitoring response to therapy in clinical trials and routine patient care.…”

Section: Introductionmentioning

confidence: 99%

Clinical laboratory reference values in adults in Kisumu County, Western Kenya; hematology, chemistry and CD4

et al. 2021

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Background Clinical laboratory reference intervals (RIs) are essential for diagnosing and managing patients in routine clinical care as well as establishing eligibility criteria and defining adverse events in clinical trials, but may vary by age, gender, genetics, nutrition and geographic location. It is, therefore, critical to establish region-specific reference values in order to inform clinical decision-making. Methods We analyzed data from a prospective observational HIV incidence cohort study in Kombewa, Kenya. Study participants were healthy males and females, aged 18–35 years, without HIV. Median and 95% reference values (2.5th percentile to 97.5th percentile) were calculated for laboratory parameters including hematology, chemistry studies, and CD4 T cell count. Standard Deviation Ratios (SDR) and Bias Ratios (BR) are presented as measures of effect magnitude. Findings were compared with those from the United States and other Kenyan studies. Results A total of 299 participants were analyzed with a median age of 24 years (interquartile range: 21–28). Ratio of males to females was 0.9:1. Hemoglobin range (2.5th—97.5th percentiles) was 12.0–17.9 g/dL and 9.5–15.3 g/dL in men and women respectively. In the cohort, MCV range was 59-95fL, WBC 3.7–9.2×103/μL, and platelet 154–401×103/μL. Chemistry values were higher in males; the creatinine RI was 59–103 μmol/L in males vs. 46–76 μmol/L in females (BRUL>.3); and the alanine transferase range was 8.8–45.3 U/L in males vs. 7.5–36.8 U/L in females (SDR>.3). The overall CD4 T cell count RI was 491–1381 cells/μL. Some parameters including hemoglobin, neutrophil, creatinine and ALT varied with that from prior studies in Kenya and the US. Conclusion This study not only provides clinical reference intervals for a population in Kisumu County but also highlights the variations in comparable settings, accentuating the requirement for region-specific reference values to improve patient care, scientific validity, and quality of clinical trials in Africa.

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confidence: 99%

Clinical laboratory reference values in adults in Kisumu County, Western Kenya; hematology, chemistry and CD4

et al. 2021

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Study design approaches for future active-controlled HIV prevention trials

Donnell,

Kansiime,

Glidden

et al. 2023

Statistical Communications in Infectious Diseases

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Objectives Vigorous discussions are ongoing about future efficacy trial designs of candidate human immunodeficiency virus (HIV) prevention interventions. The study design challenges of HIV prevention interventions are considerable given rapid evolution of the prevention landscape and evidence of multiple modalities of highly effective products; future trials will likely be ‘active-controlled’, i.e., not include a placebo arm. Thus, novel design approaches are needed to accurately assess new interventions against these highly effective active controls. Methods To discuss active control design challenges and identify solutions, an initial virtual workshop series was hosted and supported by the International AIDS Enterprise (October 2020-March 2021). Subsequent symposia discussions continue to advance these efforts. As the non-inferiority design is an important conceptual reference design for guiding active control trials, we adopt several of its principles in our proposed design approaches. Results We discuss six potential study design approaches for formally evaluating absolute prevention efficacy given data from an active-controlled HIV prevention trial including using data from: 1) a registrational cohort, 2) recency assays, 3) an external trial placebo arm, 4) a biomarker of HIV incidence/exposure, 5) an anti-retroviral drug concentration as a mediator of prevention efficacy, and 6) immune biomarkers as a mediator of prevention efficacy. Conclusions Our understanding of these proposed novel approaches to future trial designs remains incomplete and there are many future statistical research needs. Yet, each of these approaches, within the context of an active-controlled trial, have the potential to yield reliable evidence of efficacy for future biomedical interventions.

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Attaining 95-95-95 through Implementation Science: 15 Years of Insights and Best Practices from the Walter Reed Army Institute of Research’s Implementation of the U.S. President’s Emergency Plan for AIDS Relief

Cited by 2 publications

References 40 publications

Clinical laboratory reference values in adults in Kisumu County, Western Kenya; hematology, chemistry and CD4

Clinical laboratory reference values in adults in Kisumu County, Western Kenya; hematology, chemistry and CD4

Study design approaches for future active-controlled HIV prevention trials

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