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BACKGROUND:

The effect of adherence, treatment failure, and comorbidities on the cost of HIV care is not well understood.

OBJECTIVE:

To characterize the cost of HIV care including combination antiretroviral treatment (ART).

RESEARCH DESIGN:

Observational study of administrative data.

SUBJECTS:

Total 1896 randomly selected HIV-infected patients and 288 trial participants with multidrug-resistant HIV seen at the US Veterans Health Administration (VHA).

MEASURES:

Comorbidities, cost, pharmacy, and laboratory data.

RESULTS:

Many HIV-infected patients (24.5%) of the random sample did not receive ART. Outpatient pharmacy accounted for 62.8% of the costs of patients highly adherent with ART, 32.2% of the cost of those with lower adherence, and 6.2% of the cost of those not receiving ART. Compared with patients not receiving ART, high adherence was associated with lower hospital cost, but no greater total cost. Individuals with a low CD4 count (500. Most patients had medical, psychiatric, or substance abuse comorbidities. These conditions were associated with greater cost. Trial participants were less likely to have psychiatric and substance abuse comorbidities than the random sample of VHA patients with HIV.

CONCLUSIONS:

Patients receiving combination ART had higher medication costs but lower acute hospital cost. Poor control of HIV was associated with higher cost. The cost of psychiatric, substance abuse, rehabilitation, and long-term care and medications other than ART, often overlooked in HIV studies, was substantial.

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Medical Care
Authors
Mark Holodniy
Douglas K. Owens
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OBJECTIVE:

Acute HIV infection often causes influenza-like illness (ILI) and is associated with high infectivity. We estimated the effectiveness and cost-effectiveness of strategies to identify and treat acute HIV infection in men who have sex with men (MSM) in the USA.

DESIGN:

Dynamic model of HIV transmission and progression.

INTERVENTIONS:

We evaluated three testing approaches: viral load testing for individuals with ILI, expanded screening with antibody testing, and expanded screening with antibody and viral load testing. We included treatment with antiretroviral therapy for individuals identified as acutely infected.

MAIN OUTCOME MEASURES:

New HIV infections, discounted quality-adjusted life years (QALYs) and costs, and incremental cost-effectiveness ratios.

RESULTS:

At the present rate of HIV-antibody testing, we estimated that 538,000 new infections will occur among MSM over the next 20 years. Expanding antibody screening coverage to 90% of MSM annually reduces new infections by 2.8% and costs US$ 12,582 per QALY gained. Symptom-based viral load testing with ILI is more expensive than expanded antibody screening, but is more effective and costs US$ 22,786 per QALY gained. Combining expanded antibody screening with symptom-based viral load testing prevents twice as many infections compared to expanded antibody screening alone, and costs US$ 29,923 per QALY gained. Adding viral load testing to all annual HIV tests costs more than US$ 100,000 per QALY gained.

CONCLUSION:

Use of HIV viral load testing in MSM with ILI prevents more infections than does expanded annual antibody screening alone and is inexpensive relative to other screening interventions. Clinicians should consider symptom-based viral load testing in MSM, in addition to encouraging annual antibody screening.

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AIDS
Authors
Douglas K. Owens
Eran Bendavid
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BACKGROUND:

The prime-boost HIV vaccine regimen used in the recent RV144 trial resulted in modest efficacy of 31% over 3.5 years, but was substantially higher in the first year post-vaccination. We sought to explore the potential impact of a vaccine with rapidly waning efficacy in a South African population.

METHODS:

We explored two strategies using a dynamic compartmental epidemic model for heterosexual transmission of HIV: [1] vaccination of a single cohort (30%, 60% or 90% of the initial population), with exponentially waning efficacy, but booster vaccinations at 5- or 2-year intervals, and [2] continuous vaccination of the unvaccinated population at the same coverage levels (30%, 60% or 90%) but with a constant efficacy vaccine of short duration. We also examined potential changes in post-vaccination condom use.

RESULTS:

The single cohort vaccination strategies did not have a substantial impact on HIV prevalence, although without boosters they still prevented 2-6% of the expected infections at 20 years, depending on the population coverage. The 5-year and 2-year booster strategies prevented 8-24% and 17-45% of the expected infections, respectively. Continuous vaccination to maintain population coverage levels resulted in more substantial reductions in population HIV prevalence and greater numbers of infections prevented: HIV prevalence at 20 years was reduced from 23% to 8-14% and the number of expected infections was decreased by 34-59%, depending on the population coverage level. Moderate changes in post-vaccination condom use did not substantially affect these outcomes.

CONCLUSIONS:

An HIV vaccine with partial efficacy and declining protection similar to the RV144 vaccine could prevent a substantial proportion of HIV infections if booster vaccinations were effective and available. Our estimates of the population impact of vaccination would be improved by further understanding of the duration of protection, the effectiveness of booster vaccination, and whether the vaccine efficacy varies between subpopulations at higher and lower risk of exposure.

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Vaccine
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Douglas K. Owens
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The mechanism by which strictly CCR5 using HIV-1 clade C variants exacerbate disease progression in absence of coreceptor switch is not clearly known. We previously reported HIV-1 cladeC envelopes (Env) obtained from late stage Indian patients with expanded coreceptor tropism. Here we compared such Envs (having expanded coreceptor tropism) with strictly CCR5 using Envs also obtained from late stage in their capacity to utilize CD4 and CCR5 for productive entry. We found that while envelopes with low CD4 dependence tend to infect primary CD4(+) T cells better than those required optimum CD4 for entry, no significant association was found between low CD4 usage and infectivity of primary CD4(+) T cells by Env-pseudotyped viruses and theirsensitivity to CCR5 antagonist TAK-779. Interestingly, Envs that readily infected HeLa cells expressing low CD4 showed relative resistance to T20 indicating that conformational intermediates of these envelopes remained for a shorter period of time than is required for efficient inhibition by T20.

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Virus Research
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Identification of vulnerability in the HIV-1 envelope (Env) will aid in Env-based vaccine design. We recently found an HIV-1 clade C Env clone (4-2.J45) amplified from a recently infected Indian patient showing exceptional neutralization sensitivity to autologous plasma in contrast to other autologous Envs obtained at the same time point. By constructing chimeric Envs and fine mapping between sensitive and resistant Env clones, we found that substitution of highly conserved isoleucine (I) with methionine (M) (ATA to ATG) at position 424 in the C4 domain conferred enhanced neutralization sensitivity of Env-pseudotyped viruses to autologous and heterologous plasma antibodies. When tested against monoclonal antibodies targeting different sites in gp120 and gp41, Envs expressing M424 showed significant sensitivity to anti-V3 monoclonal antibodies and modestly to sCD4 and b12. Substitution of I424M in unrelated Envs also showed similar neutralization phenotype, indicating that M424 in C4 region induces exposure of neutralizing epitopes particularly in CD4 binding sites and V3 loop.

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Stanford Health Policy, 615 Crothers way, Room 222, Stanford, CA 94305-6006

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babiarz_2021.jpg MA, PhD

Dr. Babiarz’s research focuses on fertility and family planning programs, infant and maternal health, and the gender dynamics of global health. She has studied human trafficking in China and South East Asia, and currently works on quantitative approaches to issues of human trafficking and child labor in Brazil.  Dr. Babiarz specializes in large-scale program evaluations and quasi-experimental study designs. She holds a PhD in Agricultural and Resource Economics from the University of California, Davis (2011).

Sr. Research Scholar, Health Policy
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Professor, Pediatrics
Professor, Health Policy
Professor, Epidemiology & Population Health (by courtesy)
sanders_photo_20153.jpg MD, MPH

Dr. Lee Sanders is a general pediatrician and Professor of Pediatrics at the Stanford University School of Medicine, where he is Chief of the Division of General Pediatrics. He holds a joint appointment in the Center for Health Policy in the Freeman Spogli Institute for International Studies, where he is a co-director of the Center for Policy, Outcomes and Prevention (CPOP).

An author of numerous peer-reviewed articles addressing child health disparities, Dr. Sanders is a nationally recognized scholar in the fields of health literacy and child chronic-illness care.  Dr. Sanders was named a Robert Wood Johnson Foundation Generalist Physician Faculty Scholar for his leadership on the role of maternal health literacy and English-language proficiency in addressing child health disparities.  Aiming to make the US health system more navigable for the one in 4 families with limited health literacy, he has served as an advisor to the Institute of Medicine, the Centers for Disease Control and Prevention, the Food and Drug Administration, the American Academy of Pediatrics, the Academic Pediatric Association, and the American Cancer Society.  Dr. Sanders leads a multi-disciplinary CPOP research team that provides analytic guidance to national and state policies affecting children with complex chronic illness – with a focus on the special health-system requirements that arise from the unique epidemiology, care-use patterns, and health-care costs for this population.  He leads another CPOP/PCOR-based research team that applies family-centered approaches to new technologies that aim to improve care coordination for children with medical complexity.    Dr. Sanders is also principal investigator on two NIH-funded studies that address health literacy in the pediatric context: one aims to assess the efficacy of a low-literacy, early-childhood intervention designed to prevent early childhood obesity; the other aims to provide the FDA with guidance on improved labeling of pediatric liquid medication.  Research settings for this work include state and regional health departments, primary-care and subspecialty-care clinics, community-health centers, WIC offices, federally subsidized child-care centers, and family advocacy centers.

Dr. Sanders received a BA in History and Science from Harvard University, an MD from Stanford University, and a MPH from the University of California, Berkeley.  Between 2006 and 2011, Dr. Sanders served as Medical Director of Children’s Medical Services South Florida, a Florida state agency that coordinates care for more than 10,000 low-income children with special health care needs.  He was also Medical Director for Reach Out and Read Florida, a pediatric-clinic-based program that provides books and early-literacy promotion to more than 200,000 underserved children.  At the University of Miami, Dr. Sanders directed the Jay Weiss Center for Social Medicine and Health Equity, which fosters a scholarly community committed to addressing global health inequities through community-based participatory research.  At Stanford University, Dr. Sanders served as co-medical director of the Family Advocacy Program, which provides free legal assistance to help address social determinants of child health.

Fluent in Spanish, Dr. Sanders is co-director of the Complex Primary Care Clinic at Stanford Children’s Health, which provides multi-disciplinary team care for children with complex chronic conditions.  Dr. Sanders is also the father of two daughters, aged 11 and 14 years, who make sure he practices talking less and listening more.

Co-Director, Center for Policy, Outcomes & Prevention (CPOP)
Chief, Division of General Pediatrics, School of Medicine
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In the present study, we investigated genetic divergence between complete autologous HIV-1 env genes amplified directly from plasma of two anti-retroviral naïve, slow progressing Indian patients with broad neutralizing antibody response. All the envelopes (Env) clones obtained from one patient (LT1) belonged to subtype C; the second patient (LT5) harbored quasispecies comprising of pure B, C and B/C recombinants with distinct breakpoints indicative of dual infection with genetically distinct strains. Further characterization of these Envs would provide insights to the biological properties under strong humoral immune response.

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Chief of Ophthalmology for the VA Palo Alto Health Care System
Assistant Professor, VA
pershingSuzann.jpg MD, MS

Dr. Pershing is on the ophthalmology faculty at Stanford University School of Medicine and serves as Chief of Ophthalmology for the VA Palo Alto Health Care System, with an academic career blending clinical practice, teaching, research, and administration.

Her research interests focus on analyses of ophthalmic epidemiology and delivery of ophthalmic health care services, as well as improved utilization of evidence-based medicine to determine cost-effectiveness and relative outcomes of ophthalmic treatments. Through this, she aims to provide additional information to policymakers and clinicians in order to optimize treatment choices. She is also interested in health care innovation – technology as well as quality and delivery systems. Dr. Pershing is active in big data initiatives and analysis, including collaborative projects at Stanford and serving on the American Academy of Ophthalmology (AAO) IRIS registry task force and as the AAO representative to the International Consortium for Health Outcomes Measurement (ICHOM).

She graduated from university summa cum laude in 2002, and with high honors from medical school in 2006. During medical school, she was elected to the Alpha Omega Alpha national medical honor society, served as chapter president in her final year, and was honored with the President’s Clinical Science Award, Merck Award for Academic Excellence, and American Medical Women’s Association Commendation. She subsequently completed ophthalmology residency at Stanford University, followed by an AHRQ fellowship in Health Care Research and Health Policy through the Center for Health Policy/Primary Care and Outcomes Research. She presently teaches medical students at Stanford and oversees eye care services at the Palo Alto VA Medical Center.

Dr. Pershing also serves on the national board of directors of the Alpha Omega Alpha medical honor society, with focus on resident initiatives, and mentors both medical students and undergraduate students (through the Stanford Immersion in Medicine series and VA clinical internships in ophthalmology). Dr. Pershing has had an interest in teaching since tutoring fellow students in college and medical school. She is currently co-director for the medical student ophthalmology clerkships, Ophth 300A and 301A and works with students on directed ophthalmology research and MedScholars projects.

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