Dean Winslow

All Publications

• The hospital medicine-infectious diseases career path: Opportunities and insights. Journal of hospital medicine Wang, M. E., Winslow, D. L., Shah, S. S. 2024

  View details for DOI 10.1002/jhm.13513

  View details for PubMedID 39363507

• Is early initiation of antiretroviral therapy important? AIDS (London, England) Winslow, D. L. 2024; 38 (8): 1263-1264

  View details for DOI 10.1097/QAD.0000000000003898

  View details for PubMedID 38814713

• Predicting tuberculosis at antiretroviral therapy initiation: the combination of monocyte-to-lymphocyte ratio and hemoglobin level may be a key. AIDS (London, England) Tsukamoto, T., Winslow, D. L. 2024; 38 (1): 115-117

  View details for DOI 10.1097/QAD.0000000000003736

  View details for PubMedID 38061021

• Improving Sepsis Outcomes in the Era of Pay-for-Performance and Electronic Quality Measures: A Joint IDSA/ACEP/PIDS/SHEA/SHM/SIDP Position Paper. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Rhee, C., Strich, J. R., Chiotos, K., Classen, D. C., Cosgrove, S. E., Greeno, R., Heil, E. L., Kadri, S. S., Kalil, A. C., Gilbert, D. N., Masur, H., Septimus, E. J., Sweeney, D. A., Terry, A., Winslow, D. L., Yealy, D. M., Klompas, M. 2023

  Abstract

  The Centers for Medicare & Medicaid Services (CMS) introduced the Severe Sepsis/Septic Shock Management Bundle (SEP-1) as a pay-for-reporting measure in 2015 and is now planning to make it a pay-for-performance measure by incorporating it into the Hospital Value-Based Purchasing Program. This joint IDSA/ACEP/PIDS/SHEA/SHM/SIPD position paper highlights concerns with this change. Multiple studies indicate that SEP-1 implementation was associated with increased broad-spectrum antibiotic use, lactate measurements, and aggressive fluid resuscitation for patients with suspected sepsis but not with decreased mortality rates. Increased focus on SEP-1 risks further diverting attention and resources from more effective measures and comprehensive sepsis care. We recommend retiring SEP-1 rather than using it in a payment model and shifting instead to new sepsis metrics that focus on patient outcomes. CMS is developing a community-onset sepsis 30-day mortality electronic clinical quality measure (eCQM) that is an important step in this direction. The eCQM preliminarily identifies sepsis using systemic inflammatory response syndrome (SIRS) criteria, antibiotic administrations or diagnosis codes for infection or sepsis, and clinical indicators of acute organ dysfunction. We support the eCQM but recommend removing SIRS criteria and diagnosis codes to streamline implementation, decrease variability between hospitals, maintain vigilance for patients with sepsis but without SIRS, and avoid promoting antibiotic use in uninfected patients with SIRS. We further advocate for CMS to harmonize the eCQM with the Centers for Disease Control and Prevention's (CDC) Adult Sepsis Event surveillance metric to promote unity in federal measures, decrease reporting burden for hospitals, and facilitate shared prevention initiatives. These steps will result in a more robust measure that will encourage hospitals to pay more attention to the full breadth of sepsis care, stimulate new innovations in diagnosis and treatment, and ultimately bring us closer to our shared goal of improving outcomes for patients.

  View details for DOI 10.1093/cid/ciad447

  View details for PubMedID 37831591

• Honor Detail-Baghdad 2008. Military medicine Winslow, D. L. 2023

  View details for DOI 10.1093/milmed/usad275

  View details for PubMedID 37522737

• SARS-CoV-2 outbreak among staff and evacuees at Operation Allies Welcome Safe Havens. Public health nursing (Boston, Mass.) Meeker, J. R., Gosdin, L., Siu, A., Turner, L., Zusman, B. D., Sadigh, K. S., Carpenter, R., Dopson, S., Saindon, J., Kyaw, N. T., Segaloff, H. E., Pritchard, N., Shahum, A., Traboulsi, R., Worrell, M. C., Beaucham, C., Gandhi, P., Winslow, D. L., Rotz, L., Talley, L., Mosites, E., Boyd, A. T. 2023

  Abstract

  We report on five SARS-CoV-2 congregate setting outbreaks at U.S. Operation Allies Welcome Safe Havens/military facilities. Outbreak data were collected, and attack rates were calculated for various populations. Even in vaccinated populations, there was rapid spread, illustrating the importance of institutional prevention and mitigation policies in congregate settings.

  View details for DOI 10.1111/phn.13227

  View details for PubMedID 37462182

• Complexities of rifamycin use in persons with HIV infection. AIDS (London, England) Nguyen, N. N., Winslow, D. L. 2023; 37 (7): 1161-1163

  View details for DOI 10.1097/QAD.0000000000003542

  View details for PubMedID 37139651

• Distinct inflammatory profiles linked to cardiovascular disease risk in HIV infection: implications for the design of preventive and therapeutic interventions. AIDS (London, England) Laurence, J., Winslow, D. L. 2023; 37 (4): 693-695

  View details for DOI 10.1097/QAD.0000000000003475

  View details for PubMedID 36815523

• COVID-19 vaccines for the military? Here’s what George Washington would have done. Winslow, D. L. San Francisco Chronicle. 2023
• Addressing the burden of HIV-associated chronic lung disease in West Africa. AIDS (London, England) Collini, P., Winslow, D. L. 2022; 36 (14): 2075-2076

  View details for DOI 10.1097/QAD.0000000000003390

  View details for PubMedID 36305187

• New onset kidney impairment in a large pre-exposure prophylaxis demonstration project in New South Wales, Australia. AIDS (London, England) Lucas, G. M., Winslow, D. L. 2021; 35 (14): 2395-2397

  View details for DOI 10.1097/QAD.0000000000003077

  View details for PubMedID 34723855

• Pediatric liquid 'single tablet regimens' for HIV-a call to action. AIDS (London, England) Winslow, D. L. 2021; 35 (9): 1497-1498

  View details for DOI 10.1097/QAD.0000000000002885

  View details for PubMedID 34185714

• David Katzenstein and James Hakim-In Memoriam. AIDS (London, England) Campbell, T., Kassaye, S., Winslow, D. L. 2021; 35 (8): 1331-1332

  View details for DOI 10.1097/QAD.0000000000002924

  View details for PubMedID 34076621

• Peginterferon Lambda-1a for treatment of outpatients with uncomplicated COVID-19: a randomized placebo-controlled trial. Nature communications Jagannathan, P. n., Andrews, J. R., Bonilla, H. n., Hedlin, H. n., Jacobson, K. B., Balasubramanian, V. n., Purington, N. n., Kamble, S. n., de Vries, C. R., Quintero, O. n., Feng, K. n., Ley, C. n., Winslow, D. n., Newberry, J. n., Edwards, K. n., Hislop, C. n., Choong, I. n., Maldonado, Y. n., Glenn, J. n., Bhatt, A. n., Blish, C. n., Wang, T. n., Khosla, C. n., Pinsky, B. A., Desai, M. n., Parsonnet, J. n., Singh, U. n. 2021; 12 (1): 1967

  Abstract

  Type III interferons have been touted as promising therapeutics in outpatients with coronavirus disease 2019 (COVID-19). We conducted a randomized, single-blind, placebo-controlled trial (NCT04331899) in 120 outpatients with mild to moderate COVID-19 to determine whether a single, 180 mcg subcutaneous dose of Peginterferon Lambda-1a (Lambda) within 72 hours of diagnosis could shorten the duration of viral shedding (primary endpoint) or symptoms (secondary endpoint). In both the 60 patients receiving Lambda and 60 receiving placebo, the median time to cessation of viral shedding was 7 days (hazard ratio [HR] = 0.81; 95% confidence interval [CI] 0.56 to 1.19). Symptoms resolved in 8 and 9 days in Lambda and placebo, respectively, and symptom duration did not differ significantly between groups (HR 0.94; 95% CI 0.64 to 1.39). Both Lambda and placebo were well-tolerated, though liver transaminase elevations were more common in the Lambda vs. placebo arm (15/60 vs 5/60; p = 0.027). In this study, a single dose of subcutaneous Peginterferon Lambda-1a neither shortened the duration of SARS-CoV-2 viral shedding nor improved symptoms in outpatients with uncomplicated COVID-19.

  View details for DOI 10.1038/s41467-021-22177-1

  View details for PubMedID 33785743

• Hepatitis C virus infection and cardiac dysfunction in women. AIDS (London, England) Winslow, D. L. 2021; 35 (10): 1689-1690

  View details for DOI 10.1097/QAD.0000000000002938

  View details for PubMedID 34270491

• Suppurative lymphadenitis caused by hypermucoid-variant Klebsiella in a Polynesian woman: a case report. Diagnostic microbiology and infectious disease Sun, B., Singhal, S., Winslow, D. L. 2020; 98 (4): 115166

  Abstract

  Hypermucoid Klebsiella pneumoniae, known for its association with multiple-organ infection, has gradually increased in prevalence beyond where it was first characterized in East Asia. Here we describe a unique presentation of suppurative lymphadenitis due to hypermucoid Klebsiella in a patient from Tonga, a country with few reported cases.

  View details for DOI 10.1016/j.diagmicrobio.2020.115166

  View details for PubMedID 32889418

• Impact of Sepsis Mandates on Sepsis Care: Unintended Consequences. The Journal of infectious diseases Swenson, K. E., Winslow, D. L. 2020; 222 (Supplement_2): S166–S173

  Abstract

  The creation of dedicated sepsis guidelines and their broad dissemination over the past 2 decades have contributed to significant improvements in sepsis care. These successes have spurred the creation of bundled care mandates by major healthcare payers, such as the Center for Medicare and Medicaid Services. However, despite the likely benefits of guideline-directed sepsis bundles, mandated treatments in sepsis may lead to unintended consequences as the standard of care in sepsis improves. In particular, the heterogeneous spectrum of presentation and disease severity in sepsis, as well as the complexity surrounding the benefits of specific interventions in sepsis, argues for an individualized and titrated approach to interventions: an approach generally not afforded by care mandates. In this review, we review the risks and benefits of mandated care for sepsis, with particular emphasis on the potential adverse consequences of common bundle components such as early empiric antibiotics, weight-based fluid administration, and serum lactate monitoring. Unlike guideline-directed care, mandated care in sepsis precludes providers from tailoring treatments to heterogeneous clinical scenarios and may lead to unintended harms for individual patients.

  View details for DOI 10.1093/infdis/jiaa133

  View details for PubMedID 32691831

• Infectious Diseases Society of America Position Paper: Recommended Revisions to the National Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) Sepsis Quality Measure. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Rhee, C., Chiotos, K., Cosgrove, S. E., Heil, E. L., Kadri, S. S., Kalil, A. C., Gilbert, D. N., Masur, H., Septimus, E. J., Sweeney, D. A., Strich, J. R., Winslow, D. L., Klompas, M. 2020

  Abstract

  The Centers for Medicare & Medicaid Services' Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) measure has appropriately established sepsis as a national priority. However, the Infectious Diseases Society of America (IDSA and five additional endorsing societies) is concerned about SEP-1's potential to drive antibiotic overuse because it does not account for the high rate of sepsis overdiagnosis and encourages aggressive antibiotics for all patients with possible sepsis, regardless of the certainty of diagnosis or severity of illness. IDSA is also concerned that SEP-1's complex "time zero" definition is not evidence-based and is prone to inter-observer variation. In this position paper, IDSA outlines several recommendations aimed at reducing the risk of unintended consequences of SEP-1 while maintaining focus on its evidence-based elements. IDSA's core recommendation is to limit SEP-1 to septic shock, for which the evidence supporting the benefit of immediate antibiotics is greatest. Prompt empiric antibiotics are often appropriate for suspected sepsis without shock, but IDSA believes there is too much heterogeneity and difficulty defining this population, uncertainty about the presence of infection, and insufficient data on the necessity of immediate antibiotics to support a mandatory treatment standard for all patients in this category. IDSA believes guidance on managing possible sepsis without shock is more appropriate for guidelines that can delineate the strengths and limitations of supporting evidence and allow clinicians discretion in applying specific recommendations to individual patients. Removing sepsis without shock from SEP-1 will mitigate the risk of unnecessary antibiotic prescribing for noninfectious syndromes, simplify data abstraction, increase measure reliability, and focus attention on the population most likely to benefit from immediate empiric broad-spectrum antibiotics.

  View details for DOI 10.1093/cid/ciaa059

  View details for PubMedID 32374861

• Why we need the assault weapons ban of 2019 Winslow, D. L. San Jose Mercury News. 2019
• Reply to Al-Hasan and Justo. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Kalil, A. C., Gilbert, D. N., Winslow, D. L., Masur, H. n., Klompas, M. n. 2019; 68 (8): 1432

  View details for PubMedID 30102343

• Veteran: Betrayal of the Kurds dishonors the sacrifices of soldiers who gave their lives Winslow, D. San Francisco Chronicle. 2019
• Acute Kidney Injury Due to Systemic Absorption of Antibiotics Impregnated in a Bone Cement Spacer: An Underrecognized Complication of a Common Intervention INFECTIOUS DISEASES IN CLINICAL PRACTICE Nakasone, T. S., Multani, A., Chary, A., Renault, C. A., Winslow, D. L. 2018; 26 (5): 291–93

  View details for DOI 10.1097/IPC.0000000000000575

  View details for Web of Science ID 000444393100022

• Seroconversion on preexposure prophylaxis AIDS Rizzardini, G., Winslow, D. L. 2018; 32 (9): 1199–1200

  View details for PubMedID 29746319

• Infectious Diseases Society of America (IDSA) POSITION STATEMENT: Why IDSA Did Not Endorse the Surviving Sepsis Campaign Guidelines CLINICAL INFECTIOUS DISEASES Kalil, A. C., Gilbert, D. N., Winslow, D. L., Masur, H., Klompas, M., IDSA Sepsis Task Force 2018; 66 (10): 1631–35

  Abstract

  IDSA did not endorse the 2016 Surviving Sepsis Campaign Guidelines despite being represented in the working group that drafted the guidelines document. Leadership from the IDSA, the Surviving Sepsis Campaign Guidelines, and the Society of Critical Care Medicine had numerous amicable discussions primarily regarding the bolded, rated guidelines recommendations. Our societies had different perspectives, however, regarding the interpretation of the major studies that informed the guidelines' recommendations, thus leading us to different conclusions and different perspectives on the recommendations. IDSA consequently elected not to endorse the guidelines. IDSA nonetheless hopes to be able to continue collaborating with the Surviving Sepsis Campaign and the Society of Critical Care Medicine to resolve our differences and to develop further strategies together to prevent sepsis and septic shock as well as reduce death and disability from these conditions both nationally and globally.

  View details for DOI 10.1093/cid/cix997

  View details for Web of Science ID 000432184200027

  View details for PubMedID 29182749

• "I spoke my mind on guns. Then my Senate confirmation was put on hold". Washington Post Op/Ed Winslow, D. Washington Post. Washington Post. 2017

  Abstract

  Winslow, Dean (20 December 2017). "I spoke my mind on guns. Then my Senate confirmation was put on hold". Washington Post. Retrieved 21 December 2017.

• Treatment as prevention: some additional thoughts AIDS Detels, R., Winslow, D. L. 2012; 26 (4): 519-520

  View details for DOI 10.1097/QAD.0b013e32834fa17e

  View details for Web of Science ID 000300411500015

  View details for PubMedID 22156975

• HIV AND THE HOMELESS: THE EFFECTS OF HOUSING STATUS ON HIV DISEASE PROGRESSION AND HEALTHCARE ACCESS Shelby, S., Ho, C., Brooks, E., Winslow, D., Kamal, A., Doorley, S. SPRINGER. 2011: S52–S53

  View details for Web of Science ID 000208812700091

• Efavirenz Plasma Concentrations and Cytochrome 2B6 Polymorphisms ANNALS OF PHARMACOTHERAPY Lindfelt, T., O'Brien, J., Song, J. C., Patel, R., Winslow, D. L. 2010; 44 (10): 1572-1578

  Abstract

  Interpatient variability in efavirenz concentrations may be due to CYP2B6 genetic polymorphisms. Efavirenz concentration and pharmacogenomic data are scarce in Latino patients.To evaluate the difference in trough and midpoint efavirenz plasma concentrations between HIV-positive Latino and white patients. In addition, this study evaluated the association between efavirenz concentrations and CYP2B6 polymorphisms in Latino and white HIV-positive subjects.This pilot study included 10 Latinos and 10 whites. Two efavirenz blood concentrations were determined: a trough and a midpoint. CYP2B6 genetic polymorphisms were analyzed at the 516 (G to T) and 785 (A to G) codons. The Mann-Whitney test was used to determine whether efavirenz concentrations varied with ethnicity. The Kruskal-Wallis test was used to determine whether efavirenz concentrations varied with CYP2B6 genetic polymorphisms. Efavirenz concentrations were expressed as medians (minimum, maximum).Midpoint concentrations were 1.58 μg/mL (1.36, 6.02) and 3.14 μg/mL (1.74, 7.72) for whites and Latinos, respectively (p < 0.05). Trough concentrations did not vary as a function of ethnicity. Ten percent of Latinos and whites tested positive for homozygous variants of CYP2B6-516 and CYP2B6-785. One white subject tested positive for the homozygous variant of CYP2B6-1459. Trough concentrations for 516TT, 516GT, and 516GG (wild type) were 5.13 μg/mL (4.13, 6.12), 2.13 μg/mL (1.33, 3.37), and 1.44 μg/mL (0.59, 2.92), respectively (p < 0.05). Trough concentrations for 785GG, 785AG, and 785AA (wild type) were 5.12 μg/mL (4.13, 6.12), 1.98 μg/mL (1.33, 3.37), and 1.27 μg/mL (0.59, 2.92), respectively (p < 0.05). None of the patients took concomitant medications that impacted CYP2B6 metabolism.Trough efavirenz concentrations were significantly higher in patients with the 785 (A to G) and 516 (G to T) variants. Midpoint efavirenz concentrations in Latinos were significantly higher than those of whites.

  View details for DOI 10.1345/aph.1P141

  View details for Web of Science ID 000282675100006

  View details for PubMedID 20841522

• Gross Hematuria in a Young Iraqi Man - Diagnosis: infection due to Schistosoma haematobium CLINICAL INFECTIOUS DISEASES Van Horn, G. T., Goodrich, A., Winslow, D. L. 2010; 50 (8): 1144-?

  View details for DOI 10.1086/651270

  View details for Web of Science ID 000275645900017

  View details for PubMedID 20233043

• Replication Capacity of HIV-1 in the Presence of Resistance-Associated Substitutions in Protease CLINICAL INFECTIOUS DISEASES Winslow, D. L. 2009; 49 (1): 165–66

  View details for DOI 10.1086/599619

  View details for Web of Science ID 000266766500024

  View details for PubMedID 19500032

• Efavirenz-induced hypersensitivity reaction manifesting in rash and hepatitis in a Latino male ANNALS OF PHARMACOTHERAPY Leung, J. M., O'Brien, J. G., Wong, H. K., Winslow, D. L. 2008; 42 (3): 425-429

  Abstract

  To report a case of hypersensitivity manifesting in a rash, fever, and life-threatening hepatitis in a patient initiated on efavirenz therapy.A 30-year-old Latino male newly diagnosed with HIV was started on efavirenz-based highly active antiretroviral therapy (HAART) using tenofovir 300 mg, emtricitabine 200 mg, and efavirenz 600 mg once daily. Eleven days after beginning therapy, he developed a hypersensitivity reaction manifesting in rash and fever preceding severe drug-induced hepatitis. Liver enzyme peak values were aspartate transaminase 3410 U/L and alanine transaminase 2132 U/L. Hepatitis resolved with discontinuation of the HAART. The patient was rechallenged with tenofovir and emtricitabine one year later; no adverse reactions occurred.The Naranjo probability scale demonstrated a probable relationship between this adverse reaction and efavirenz. A MEDLINE search (2004 to September 2007) revealed 2 cases of rash preceding hepatitis with the initiation of efavirenz. Both cases were in women; there were no prior reported cases of efavirenz hypersensitivity in men. Although the mechanism of this reaction is unknown, a few factors may have contributed to this reaction. The half-life and the auto-induction of efavirenz may explain the continued rise in liver enzymes and severe hepatitis that continued to occur once the drug was discontinued. Another cause that may have contributed is the metabolism of the medication. CYP2B6 is responsible for almost 90% of the clearance of efavirenz. Data from a recent pharmacokinetic study showed that efavirenz concentrations were higher in both black and Latino patients when compared with those of white patients. In addition, it is highly probable that this patient's liver function was impaired when transaminase levels peaked, resulting in decreased clearance of efavirenz.Although such a hypersensitivity reaction is rare, efavirenz is the most probable cause of the erythematous maculopapular rash and acute hepatitis in this patient. Monitoring of liver function in patients who present with a rash following initiation of efavirenz-based HAART is recommended. In addition, clinicians should exercise caution in patients presenting with rash, fever, and increased liver enzymes (> 3 times the upper limit of normal or patient baseline). It is strongly recommended that efavirenz therapy be withheld in such cases and reevaluated once liver enzyme levels stabilize.

  View details for DOI 10.1345/aph.1K574

  View details for Web of Science ID 000254000200017

  View details for PubMedID 18252833

• Treating the enemy. Annals of internal medicine Winslow, D. L. 2007; 147 (4): 278-279

  View details for PubMedID 17709761

• Wind, rain, flooding, and fear: Coordinating military public health in the aftermath of Hurricane Katrina CLINICAL INFECTIOUS DISEASES Winslow, D. L. 2005; 41 (12): 1759-1763

  Abstract

  On 29 August 2005, a category 4 hurricane struck the Gulf Coast of Mississippi and southeast Louisiana, resulting in widespread destruction caused by winds in excess of 190 km/h (120 miles/h), heavy rain, and flooding. Communication, electricity, and fresh water supplies were disrupted throughout the region, rendering much of the area uninhabitable. Despite tremendous obstacles, the US military spearheaded the eventually successful rescue, recovery, and relief operations. This article describes the challenges of protecting the health and safety of these personnel in the immediate aftermath of Hurricane Katrina.

  View details for Web of Science ID 000233698300012

  View details for PubMedID 16288401

• HIV-1 protease and reverse transcriptase mutation patterns responsible for discordances between genotypic drug resistance interpretation algorithms JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES Ravela, J., Betts, B. J., Brun-Vezinet, F., Vandamme, A. M., Descamps, T., Van Laethem, K., Smith, K., Schapiro, J. M., Winslow, D. L., Reid, C., Shafer, R. W. 2003; 33 (1): 8-14

  Abstract

  Several rules-based algorithms have been developed to interpret results of HIV-1 genotypic resistance tests. To assess the concordance of these algorithms and to identify sequences causing interalgorithm discordances, we applied four publicly available algorithms to the sequences of isolates from 2,045 individuals in northern California. Drug resistance interpretations were classified as S for susceptible, I for intermediate, and R for resistant. Of 30,675 interpretations (2,045 sequences x 15 drugs), 4.4% were completely discordant, with at least one algorithm assigning an S and another an R; 29.2% were partially discordant, with at least one algorithm assigning an S and another an I, or at least one algorithm assigning an I and another an R; and 66.4% displayed complete concordance, with all four algorithms assigning the same interpretation. Discordances between nucleoside reverse transcriptase inhibitor interpretations usually resulted from several simple, frequently occurring mutational patterns. Discordances between protease inhibitor interpretations resulted from a larger number of more complex mutation patterns. Discordances between nonnucleoside reverse transcriptase inhibitor interpretations were uncommon and resulted from a small number of individual drug resistance mutations. Determining the clinical significance of these mutation patterns responsible for interalgorithm discordances will improve interalgorithm concordance and the accuracy of genotypic resistance interpretation.

  View details for Web of Science ID 000182805400002

  View details for PubMedID 12792349

• Accuracy of the TRUGENE HIV-1 genotyping kit JOURNAL OF CLINICAL MICROBIOLOGY Grant, R. M., Kuritzkes, D. R., JOHNSON, V. A., Mellors, J. W., Sullivan, J. L., Swanstrom, R., D'Aquila, R. T., van Gorder, M., Holodniy, M., Lloyd, R. M., Reid, C., Morgan, G. F., Winslow, D. L. 2003; 41 (4): 1586-1593

  Abstract

  Drug resistance and poor virological responses are associated with well-characterized mutations in the viral reading frames that encode the proteins that are targeted by currently available antiretroviral drugs. An integrated system was developed that includes target gene amplification, DNA sequencing chemistry (TRUGENE HIV-1 Genotyping Kit), and hardware and interpretative software (the OpenGene DNA Sequencing System) for detection of mutations in the human immunodeficiency virus type 1 (HIV-1) protease and reverse transcriptase sequences. The integrated system incorporates reverse transcription-PCR from extracted HIV-1 RNA, a coupled amplification and sequencing step (CLIP), polyacrylamide gel electrophoresis, semiautomated analysis of data, and generation of an interpretative report. To assess the accuracy and robustness of the assay system, 270 coded plasma specimens derived from nine patients were sent to six laboratories for blinded analysis. All specimens contained HIV-1 subtype B viruses. Results of 270 independent assays were compared to "gold standard" consensus sequences of the virus populations determined by sequence analysis of 16 to 20 clones of viral DNA amplicons derived from two independent PCRs using primers not used in the kit. The accuracy of the integrated system for nucleotide base identification was 98.7%, and the accuracy for codon identification at 54 sites associated with drug resistance was 97.6%. In a separate analysis of plasma spiked with infectious molecular clones, the assay reproducibly detected all 72 different drug resistance mutations that were evaluated. There were no significant differences in accuracy between laboratories, between technologists, between kit lots, or between days. This integrated assay system for the detection of HIV-1 drug resistance mutations has a high degree of accuracy and reproducibility in several laboratories.

  View details for DOI 10.1128/JCM.41.4.1586-1593.2003

  View details for Web of Science ID 000182179900037

  View details for PubMedID 12682149

  View details for PubMedCentralID PMC153856

• Clinical resistance patterns and responses to two sequential protease inhibitor regimens in saquinavir and reverse transcriptase inhibitor-experienced persons 5th Conference on Retroviruses and Opportunistic Infections Lawrence, J., Schapiro, J., Winters, M., Montoya, J., Zolopa, A., Pesano, R., Efron, B., Winslow, D., Merigan, T. C. UNIV CHICAGO PRESS. 1999: 1356–64

  Abstract

  The efficacy of sequential protease inhibitor therapy was studied in 16 human immunodeficiency virus (HIV) 1-infected persons in whom saquinavir with multiple nucleoside reverse transcriptase (RT) inhibitors (NRTI) had failed. Nelfinavir plus two NRTIs (new or continued) resulted in minimal (0.59 log RNA copies/mL) and transient (8 weeks) suppression of plasma HIV RNA levels. Rapid failure was surprisingly associated with baseline presence of protease gene mutation L90M (P=.04) in the absence of D30N and with RT mutations D67N (P<.01), K70R/S (P=.02), and K219Q/W/R/E (P<.01). Ten patients were subsequently switched to indinavir plus nevirapine and 2 NRTIs, resulting in a median 1.62 log reduction in plasma HIV RNA, with 3 patients maintaining 400 copies/mL for 24 weeks. These results suggest that nelfinavir may have limited utility after saquinavir failure, particularly without potent concomitant therapy. Combining an NRTI with a new protease inhibitor for rescue may improve response.

  View details for Web of Science ID 000080561100007

  View details for PubMedID 10228055