Bio

Bio


My research focuses on antiretroviral therapy and complications of HIV including immune reconstitution inflammatory disease, osteoporosis, and cardiovascular disease.

Clinical Focus


  • Infectious Disease

Academic Appointments


Professional Education


  • Residency:University of Washington Medical Center (2003) WA
  • Internship:University of Washington Medical Center (2001) WA
  • Medical Education:Univ of California San Francisco (2000) CA
  • Fellowship:Stanford University - Infectious Diseases (2010) CA
  • Fellowship:Stanford University - Infectious Diseases (2008) CA
  • Board Certification: Infectious Disease, American Board of Internal Medicine (2008)

Research & Scholarship

Clinical Trials


  • Safety of and Immune Response to an Investigational HIV-1 Vaccine With or Without Interleukin-12 (IL-12) in HIV-1 Infected Adults Not Recruiting

    Therapeutic HIV vaccines are designed to control HIV infection by boosting the body's natural immune response. There are currently no FDA-approved therapeutic HIV vaccines. This study will test whether giving an HIV-1 vaccine together with or without interleukin 12 (IL-12) is safe and effective. This study will also test a new way of giving the vaccine called electroporation (EP).

    Stanford is currently not accepting patients for this trial.

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  • A Study to Treat Subjects With Telaprevir, Ribavirin, and Peginterferon Who Are Coinfected With HIV and Hepatitis C Virus (HCV) Not Recruiting

    The purpose of this study is to treat HIV and HCV coinfected subjects with telaprevir, peg-interferon alfa-2a, and ribavirin to achieve undetectable HCV RNA 12 weeks after the last planned dose of study drug.

    Stanford is currently not accepting patients for this trial. For more information, please contact Debbie Slamowitz, (650) 723-2804.

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  • Stanford Universities: The Stanford HIV Aging Cohort Recruiting

    A research study to evaluate the effect of aging and HIV on neurocognitive dysfunction (declining ability to process information), physical frailty and heart disease. HIV-infected participants whose virus is controlled on antiretroviral medications will be studied to determine the rates and risk factors of developing these conditions.

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  • Bone, Immunologic, and Virologic Effects of a Antiretroviral Regimen Not Recruiting

    There are now several HIV treatment options for a person with HIV infection who has not yet been treated. Most people who receive treatment and take their medications as directed have a good result. This is usually determined by measuring the amount of HIV in the blood (viral load). The best response is when HIV cannot be found (less than 50 copies/mL) in the blood. However, it has recently become clear that some people with HIV who are receiving effective HIV drugs continue to have more health problems than people without HIV infection. Sometimes, there is damage to organs in the body, including bone, kidneys, and the brain. The main purpose of this study is to compare the effects on bones of the following two drug combinations: - maraviroc (MVC), emtricitabine (FTC), plus darunavir/ritonavir (DRV/r) - tenofovir (TDF) plus emtricitabine (FTC) plus darunavir/ritonavir (DRV/r) Additional reasons this study is being done are the following: - To see how the drug combinations affect the brain and kidneys. - To see how well the drug combinations lower the HIV viral load. - To see how safe the drug combinations are, how well people are able to take the study drug combinations, and how well their immune systems respond to the study drugs. - To see how well the drug combinations get into the blood.

    Stanford is currently not accepting patients for this trial. For more information, please contact Debbie Slamowitz, RN, BSN, ACRN, (650) 723-2804.

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  • Safety and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/GS-7340 Single Tablet Regimen Versus Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Single Tablet Regimen in HIV 1 Infected, Antiretroviral Treatment-Naive Adults Not Recruiting

    This study is to evaluate the safety, efficacy, and tolerability of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) single tablet regimen (STR) versus E/C/F/tenofovir disoproxil fumarate (TDF; E/C/F/TDF) STR in HIV-1 infected, antiretroviral treatment-naive adults as determined by the achievement of HIV-1 RNA < 50 copies/mL at Week 24.

    Stanford is currently not accepting patients for this trial. For more information, please contact Debbie Slamowitz, (650) 723-8014.

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  • Evaluating the Effectiveness of the Quadrivalent Human Papillomavirus (HPV) Vaccine at Preventing Anal HPV Infection in HIV-Infected Men and Women Recruiting

    Men who have sex with men (MSM) have an increased risk of developing anal human papillomavirus (HPV) infections, which can be a risk factor for anal cancer. HIV-infected women are also at risk of anal cancer. This study will evaluate the effectiveness of the Food and Drug Administration (FDA)-approved quadrivalent HPV vaccine, Gardasil, at preventing anal HPV infection in HIV-infected MSM and HIV-infected women.

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  • Phase 3b Open Label Study to Evaluate Switching From Regimens Consisting of a Ritonavir-boosted Protease Inhibitor Plus Emtricitabine/Tenofovir Fixed-Dose Combination to the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF Single-Tablet Regimen in Virologically Suppressed, HIV 1 Infected Patients Not Recruiting

    To evaluate the non-inferiority of Elvitegravir/Cobicistat/ Emtricitabine/Tenofovir Disoproxil Fumarate Single-Tablet Regimen (EVG/COBI/FTC/TDF) relative to regimens consisting of a ritonavir-boosted protease inhibitor (PI/r) plus Emtricitabine/Tenofovir Fixed-Dose Combination (FTC/TDF, Truvada) in maintaining HIV 1 RNA < 50 copies/mL at Week 48 in virologically suppressed, HIV 1 infected subjects.

    Stanford is currently not accepting patients for this trial. For more information, please contact Debbie Slamowitz, 7232804.

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  • High Dose Vitamin D and Calcium for Bone Health in Individuals Initiating HAART Not Recruiting

    This study was done with people who were infected with HIV and needed to start treatment for their HIV disease. The purpose of this study is to see if taking vitamin D and calcium will help prevent the bone loss that sometimes happens when people start HIV treatment. For this study, the following HIV treatment (or HAART) were provided in the form of a single tablet that contains three different drugs: efavirenz/emtricitabine/tenofovir (EFV/FTC/TDF). These drugs are approved by the FDA to treat HIV infection. The HIV treatment provided is common for people who are taking HIV drugs for the first time. The risks seen with this HIV treatment are the same that you would encounter when taking these drugs outside of the study. The lists of risks of this HIV treatment are included in this document because the drugs are provided by the study, not because the drugs are being tested. The purpose of the study is only to look at the impact of high doses of vitamin D and calcium in preventing bone loss. There are no study objectives related to HIV treatment (EFV/FTC/TDF).

    Stanford is currently not accepting patients for this trial. For more information, please contact Debbie Slamowitz, 650-723-2804.

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  • Investigation of The Effect of Cenicriviroc (CVC) Plus FTC/TDF on Cardiovascular Disease Risk Factors Not Recruiting

    This is a single-site substudy, "Investigation of the Effect of Cenicriviroc (CVC) plus Emtricitabine/Tenofovir (FTC/TDF) on Atherosclerosis Risk Factors", open to all patients enrolled in the primary study, "A Phase 2b Randomized, Double-Blind, Double-Dummy Trial of 100 or 200 mg Once-Daily Doses of Cenicriviroc (CVC, TBR-652) or Once-Daily EFV, Each With Open-Label FTC/TDF, in HIV-1-Infected, Antiretroviral Treatment-Naïve, Adult Patients With Only CCR5-Tropic Virus", in the San Francisco Bay area to evaluate changes in brachial flow mediated dilation in patients in one of three treatment groups: 1. Cenicriviroc (CVC) at 100mg (2 tablets, 50mg each) QD + CVC matching placebo (2 tablets) QD + Efavirenz (EFV) matching placebo (1 capsule) QHS + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) (1 tablet) QD; 2. CVC at 200mg (4 tablets, 50mg each) QD + EFV matching placebo (1 capsule) QHS + FTC/TDF (1 tablet) QD; 3. CVC matching placebo (4 tablets) QD + EFV 600 mg (1 capsule) QHS + FTC/TDF (1 tablet) QD. The substudy will run for the duration of the primary study. 50 patients of the 150 total enrolled in the primary study will be referred to and enrolled in the cardiovascular substudy. Patients enrolled in the substudy and substudy protocol staff will be blinded to study treatment. Data obtained on this substudy will be analyzed in conjunction with laboratory data for cardiovascular disease risk factors and HIV-1 RNA levels obtained on the primary study. The primary study is a randomized, double-blind, double-dummy, 48-week, comparative study in approximately 150 HIV-1-infected, treatment-naïve patients with CCR5-tropic virus. Patients will be stratified by Screening HIV-1 RNA level (≥100,000 copies/mL versus <100,000 copies/mL) and randomized 2:2:1 to one of the three treatment groups. Patients will receive all medications from the primary study, and thus the primary study site will be responsible for any adverse outcomes with the drug.

    Stanford is currently not accepting patients for this trial. For more information, please contact Debbie Slamowitz, (650) 723 - 2804.

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  • A Comparative Study of Aleglitazar and Actos in Patients With Type 2 Diabetes Mellitus and Class II Heart Failure. Not Recruiting

    This 2 arm study will compare the safety, tolerability and efficacy of aleglitazar and Actos in patients with type 2 diabetes and symptomatic NYHA class II heart failure. Eligible patients will be randomized to receive either aleglitazar, titrated to an individual maximum tolerated dose up to 0.3mg p.o. daily, or Actos, titrated to an individual maximum tolerated dose up to 45mg p.o. daily, in addition to prescribed diabetes therapy where applicable. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.

    Stanford is currently not accepting patients for this trial. For more information, please contact Debbie Slamowitz, (650) 723 - 2804.

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  • Phase 3b Open-Label, Single Arm Study to Evaluate the Safety and Efficacy of Cobicistat-boosted Darunavir in HIV Infected Adults Not Recruiting

    The purpose of this study is to evaluate the safety and tolerability of cobicistat-boosted darunavir plus two fully active nucleoside analogue reverse transcriptase inhibitors in HIV 1 infected, antiretroviral treatment-naive and treatment-experienced adult subjects with no Darunavir (DRV) resistance-associated mutations.

    Stanford is currently not accepting patients for this trial. For more information, please contact Debbie Slamowitz, 650-723-2804.

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  • Study to Evaluate the Safety and Efficacy of Stribild Versus Ritonavir-Boosted Atazanavir Plus Truvada in Human Immunodeficiency Virus, Type 1 (HIV-1) Infected, Antiretroviral Treatment-Naive Adults Not Recruiting

    To evaluate the safety and efficacy of Stribild, a single tablet regimen (STR) containing fixed doses of elvitegravir (EVG)/GS-9350 (cobicistat; COBI)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) versus ritonavir-boosted atazanavir (ATV/r) plus the standard of care nucleoside reverse transcriptase inhibitor (NRTI) backbone FTC/TDF (Truvada). Ritonavir-boosted atazanavir + Truvada was selected as the active comparator for this study as it is a preferred protease inhibitor-based regimen in guidelines for the treatment of HIV-1 infected, antiretroviral treatment-naive adults.

    Stanford is currently not accepting patients for this trial. For more information, please contact Debbie Slamowitz, 650-723-2804.

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  • Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Stribild Versus Atripla in Human Immunodeficiency Virus, Type 1 (HIV-1) Infected, Antiretroviral Treatment-Naive Adults Not Recruiting

    To evaluate the safety and efficacy of Stribild, a single tablet regimen (STR) containing fixed doses of elvitegravir (EVG)/GS-9350 (cobicistat; COBI)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) versus efavirenz (EFV)/FTC/TDF (Atripla) in HIV-1 infected, antiretroviral treatment-naive adults. Stribild offers an alternative STR for patients who are not candidates for non-nucleoside reverse transcriptor (NNRTI)-based STRs.

    Stanford is currently not accepting patients for this trial. For more information, please contact Debbie Slamowitz, 650-723-2804.

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  • Open-label Safety Study of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Single-Tablet Regimen in HIV-1 Positive Patients With Mild to Moderate Renal Impairment Recruiting

    This open-label, multicenter, multi-cohort study is to assess the safety, tolerability, and efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) single-tablet regimen (STR) in treatment-naive and treatment-experienced HIV-positive, adult participants with mild to moderate renal impairment. The primary objective of this study is to evaluate the effect of E/C/F/TAF STR on renal parameters at Week 24. The proportion of subjects achieving virologic response of HIV-1 RNA < 50 copies/mL will also be assessed. At sites able to conduct the appropriate testing, approximately 30 participants will be enrolled into an intensive pharmacokinetic/pharmacodynamic (PK/PD) substudy to evaluate the PK/PD parameters of the individual components of E/C/F/TAF as well as tenofovir diphosphate (TFV-DP).

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  • Study to Evaluate the Safety and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Versus Elvitegravir/Cobicistat/Emtricitabine/ Tenofovir Disoproxil Fumarate in HIV-1 Positive, Antiretroviral Treatment-Naïve Adults Recruiting

    The purpose of this study is to evaluate the efficacy of a single-tablet regimen (STR)containing elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) versus a STR containing elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) in HIV-1 positive, antiretroviral treatment naïve adult participants as determined by the achievement of HIV-1 RNA < 50 copies/mL at Week 48.

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  • Safety and Efficacy of Darunavir/Cobicistat/Emtricitabine/GS-7340 Single Tablet Regimen Versus Cobicistat-boosted Darunavir Plus Emtricitabine/Tenofovir Disoproxil Fumarate Fixed Dose Combination in HIV-1 Infected, Antiretroviral Treatment Naive Adults Not Recruiting

    This study is to evaluate the efficacy darunavir/cobicistat/emtricitabine/GS-7340 (D/C/F/TAF) single-tablet regimen (STR) versus darunavir (DRV)+cobicistat (COBI)+emtricitabine(FTC)/tenofuvir disoproxil fumarate (TDF) in HIV-1 infected, antiretroviral treatment-naive adults as determined by the achievement of HIV-1 RNA < 50 copies/mL at Week 24.

    Stanford is currently not accepting patients for this trial. For more information, please contact Debbie Slamowitz, (650) 723-2804.

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  • Study to Evaluate the Safety and Efficacy of a Single Tablet Regimen of Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate Compared With a Single Tablet Regimen of Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naive Adults Not Recruiting

    The purpose of the study was to evaluate the safety and efficacy of the emtricitabine (FTC)/rilpivirine (RPV)/tenofovir disoproxil fumarate (TDF) single-tablet regimen (STR) compared with the efavirenz (EFV)/FTC/TDF STR in HIV-1 infected adults who had not previously received treatment with antiretroviral medications. The FTC/RPV/TDF STR offers an alternative treatment option to patients who wish to simplify or improve the tolerability of their treatment regimen. Participants were randomized in a 1:1 ratio to receive one of the study treatments. Randomization was stratified by HIV-1 RNA level (≤ 100,000 copies/mL or > 100,000 copies/mL) at screening. A treatment duration of 96 weeks was planned, with the option for subjects in FTC/RPV/TDF STR arm to receive treatment following the Week 96 visit until FTC/RPV/TDF STR is commercially available or until Gilead Sciences elects to terminate development in that country.

    Stanford is currently not accepting patients for this trial. For more information, please contact Debbie Slamowitz, (650) 723-2804.

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  • FTC/RPV/TDF on T-Cell Activation, CD4 Cell Count, Inflammatory Biomarkers and Viral Reservoir Recruiting

    This study is being done with people who are infected with HIV, but do not show any signs of having HIV. They are also feeling well without taking HIV medication and have low or undetectable levels of the virus in the blood. The purpose of this study is to see if taking HIV medication (antiretroviral therapy [ART]) will reduce immune activation (a signal that the body is fighting an infection) in people who have HIV, but do not show symptoms. Also this study will help determine how safe the drug is and how well people react to the drug. For this study, the following antiretroviral therapy (ART) will be provided in the form of a single tablet that contains three different drugs: emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF). These drugs are combined as one tablet which is approved by the Food and Drug Administration (FDA) as a single pill to treat HIV infection. The HIV medication provided is one of the recommended treatments for HIV, including people with low viral loads (how much HIV you have in your body) who are taking HIV drugs for the first time. The risks seen with this HIV medication are the same that one would encounter when taking these drugs outside of the study.

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  • Evaluating the Effectiveness of Boceprevir, Pegylated-Interferon Alfa 2b and Ribavirin in Treating Hepatitis C Virus (HCV) Infection in Adults With HIV and HCV Infection Recruiting

    Hepatitis C virus (HCV) infection is a leading cause of death and illness in people with HIV-1. Currently, the standard treatment for people with HIV-1 and HCV coinfection includes two drugs—pegylated-interferon alfa 2b (PEG-IFN) and ribavirin (RBV). The purpose of this study is to evaluate the effectiveness of giving boceprevir (BOC) together with standard treatment in treating HCV infection in people with HIV-1 and HCV coinfection.

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Publications

Journal Articles


  • TREATING PSYCHOLOGICAL TRAUMA AMONG RWANDAN ORPHANS IS ASSOCIATED WITH A REDUCTION IN HIV RISK-TAKING BEHAVIORS: A PILOT STUDY AIDS EDUCATION AND PREVENTION Talbot, A., Uwihoreye, C., Kamen, C., Grant, P., McGlynn, L., Mugabe, I., Nshimyumukiza, M., Dongier, P., Slamowitz, D., Padilla, C., Uvamahoro, J., Musayidire, I., Mukarubuga, A., Zolopa, A. 2013; 25 (6): 468-479

    Abstract

    The nongovernmental organization, Uyisenga N'Manzi (UNM), provides Rwandan orphans of genocide and HIV/AIDS with education, social, and mental health services. Many orphans in UNM report symptoms of psychological trauma. The primary study objective was to evaluate a multidisciplinary program integrating HIV prevention with an existing package of mental health services. We randomly selected 120 orphans between ages 15-25 years served by UNM and evaluated sexually-transmitted infections, HIV risk-taking behaviors and knowledge, and mental health at baseline, 5, 9, and 12 months. Increased trauma symptoms at baseline were associated with poorer coping skills and social functioning, and increased psychological distress and HIV risk-taking behavior. Following the 12-month intervention, trauma symptoms declined significantly, with those accessing counseling services showing greatest improvement. Orphans with the highest trauma scores benefited most from the intervention. In this at-risk population, addressing mental health issues in the context of HIV prevention is critical.

    View details for Web of Science ID 000327416100002

    View details for PubMedID 24245594

  • Low Baseline CD4+ Count Is Associated With Greater Bone Mineral Density Loss After Antiretroviral Therapy Initiation. Clinical infectious diseases Grant, P. M., Kitch, D., McComsey, G. A., Dube, M. P., Haubrich, R., Huang, J., Riddler, S., Tebas, P., Zolopa, A. R., Collier, A. C., Brown, T. T. 2013; 57 (10): 1483-1488

    Abstract

    Background. Bone mineral density (BMD) decreases 2%-6% in the 2 years after antiretroviral therapy (ART) initiation. Pre-ART immune deficiency and early immune recovery may contribute to this loss. Methods. We pooled data from 3 studies of ART initiation in treatment-naive patients in which serial whole-body dual-energy X-ray absorptiometry scans were performed. We used linear regression to evaluate effects of baseline CD4(+) and 16-week CD4(+) change (both absolute and relative) on 96-week total BMD change from baseline. We performed multivariable linear regression to assess associations between baseline variables of age, sex, race/ethnicity, body mass index (BMI), hepatitis C status, parent study, human immunodeficiency virus type 1 (HIV-1) RNA level, and assignment to a protease inhibitor (PI)- or tenofovir-containing regimen on 96-week total BMD change. Results. The included 796 subjects had mean 96-week total BMD loss of 2.0%. In multivariable analysis, baseline CD4(+) cell count was significantly associated with 96-week BMD loss; individuals with baseline CD4(+) <50 cells/µL lost significantly more BMD compared to those with CD4(+) ≥500 cells/µL. A greater relative, but not absolute, 16-week increase in CD4(+) count was significantly associated with greater declines in BMD, but not after controlling for baseline CD4(+) count. In multivariable analysis, older age, female sex, lower BMI, higher HIV-1 RNA levels, and PI and tenofovir assignment were also associated with greater BMD decline. Conclusions. Low pretreatment CD4(+) count, but not greater CD4(+) count increase, is a strong and independent risk factor for bone loss after ART initiation. ART initiation at higher CD4(+) counts may reduce the burden of osteoporosis and fragility fractures.

    View details for DOI 10.1093/cid/cit538

    View details for PubMedID 23943825

  • Early Virologic Response to Abacavir/Lamivudine and Tenofovir/Emtricitabine During ACTG A5202 HIV CLINICAL TRIALS Grant, P. M., Tierney, C., Budhathoki, C., Daar, E. S., Sax, P. E., Collier, A. C., Fischl, M. A., Zolopa, A. R., Balamane, M., Katzenstein, D. 2013; 14 (6): 284-291

    Abstract

    ACTG A5202 randomized treatment-naïve individuals to tenofovir-emtricitabine (TDF/FTC) or abacavir-lamivudine (ABC/3TC) combined with efavirenz (EFV) or atazanavir/ritonavir (ATV/r). Individuals in the high screening viral load (VL) stratum (≥100,000 copies/mL) had increased rates of virologic failure with ABC/3TC.To compare regimen-specific early virologic response.Using Wilcoxon rank-sum tests, we compared regimen-specific VL changes from entry to week 4 in A5202 subjects (N = 1,813) and from entry to week 1, 2, and 4 in substudy subjects (n = 179). We evaluated associations between week 4 VL change and time to virologic failure with Cox proportional hazards models.TDF/FTC and ABC/3TC produced similar week 4 VL declines in the entire study population and in the high VL stratum. EFV produced greater VL declines from baseline at week 4 than ATV/r (median -2.1 vs -1.9 log10 copies/mL; P < .001). In the substudy of subjects with week 1, 2, and 4 VL data, there was no difference in VL decline in individuals randomized to TDF/FTC versus ABC/3TC, but EFV resulted in greater VL decline from entry at each of these timepoints than ATV/r. Smaller week 4 VL decline was associated with increased risk of virologic failure.Within all treatment arms, a less robust week 4 virologic response was associated with higher risk for subsequent virologic failure. However, between-regimen differences in week 4 VL declines did not parallel the previously reported differences in longer term virologic efficacy in A5202, suggesting that between-regimen differences in responses were not due to intrinsic differences in antiviral activity.

    View details for DOI 10.1310/hct1408-284

    View details for Web of Science ID 000328443500003

    View details for PubMedID 24334181

  • Elevated Interleukin 8 and T-Helper 1 and T-Helper 17 Cytokine Levels Prior to Antiretroviral Therapy in Participants Who Developed Immune Reconstitution Inflammatory Syndrome During ACTG A5164 JOURNAL OF INFECTIOUS DISEASES Grant, P. M., Komarow, L., Lederman, M. M., Pahwa, S., Zolopa, A. R., Andersen, J., Asmuth, D. M., Devaraj, S., Pollard, R. B., Richterman, A., Kanthikeel, S., Sereti, I. 2012; 206 (11): 1715-1723

    Abstract

    Immune reconstitution inflammatory syndrome (IRIS) reflects an aberrant immune response that can develop in human immunodeficiency virus-infected patients initiating antiretroviral therapy (ART). Its pathogenesis remains unclear.We performed a nested case-control study using specimens from ACTG A5164. We compared plasma biomarkers and T-cell subsets in 19 IRIS and 39 control participants at study entry, ART initiation, and IRIS and used conditional logistic regression to develop IRIS predictive models. We evaluated the effect of corticosteroids on biomarker levels.Eleven and 8 participants developed paradoxical and unmasking IRIS, respectively, none while still receiving corticosteroids. Compared to controls, cases displayed elevations at study entry in interleukin (IL) 8, T-helper (Th) 1 (IL-2, interferon [IFN]-?, tumor necrosis factor [TNF]) and Th17 (IL-17) cytokine levels that persisted through ART initiation and IRIS. In logistic regression, baseline higher IFN-? and TNF were strong predictors of IRIS. Participants who received corticosteroids and later developed IRIS had marked increases in IL-6, IL-8, and IFN-? at the time of IRIS. T-cell activation markers did not differ in cases and controls prior to ART but were increased in cases at the time of IRIS.Increased IL-8, Th1, and Th17 cytokine levels in IRIS patients precede ART initiation and could help identify patient populations at higher risk for IRIS.

    View details for DOI 10.1093/infdis/jis604

    View details for Web of Science ID 000310968700013

    View details for PubMedID 23002445

  • When to start ART in the setting of acute AIDS-related opportunistic infections: the time is now! Current HIV/AIDS reports Grant, P. M., Zolopa, A. R. 2012; 9 (3): 251-258

    Abstract

    Despite the substantial benefits of combination antiretroviral therapy (ART), a significant proportion of HIV-infected individuals still present with advanced disease and active AIDS-related opportunistic infections (OIs). The weight of evidence from recent studies supports the early initiation of ART (ie, within 2 weeks of initiating treatment for the acute OIs). Initiating ART early in acutely ill patients can reduce AIDS-related progression and death. Early ART has not been associated with increased rates of immune reconstitution inflammatory syndrome in prospective studies of non-tuberculosis OIs, although this concern is frequently cited as a reason to delay ART. Nor has early ART been associated with increased adverse outcomes. Nonetheless, initiating ART early in acute care settings can be challenging to implement and requires a well-coordinated multidisciplinary team with expertise in ART management.

    View details for DOI 10.1007/s11904-012-0126-8

    View details for PubMedID 22733609

  • Blood (1 -> 3)-beta-D-Glucan as a Diagnostic Test for HIV-Related Pneumocystis jirovecii Pneumonia CLINICAL INFECTIOUS DISEASES Sax, P. E., Komarow, L., Finkelman, M. A., Grant, P. M., Andersen, J., Scully, E., Powderly, W. G., Zolopa, A. R. 2011; 53 (2): 197-202

    Abstract

    (See the editorial commentary by Morris and Masur, on pages 203-204.)Improved noninvasive diagnostic tests for Pneumocystis jirovecii pneumonia (PCP) are needed. We evaluated the test characteristics of plasma (1 → 3)-β-D-glucan (β-glucan) for HIV-related PCP among a large group of patients presenting with diverse opportunistic infections (OIs).The study population included all 282 participants in AIDS Clinical Trials Group A5164, a study of early versus deferred antiretroviral therapy in conjunction with initial therapy of acute OIs. Baseline plasma samples were assayed for β-glucan, with standard assay reference values defining ≥ 80 pg/mL as positive. Before this analysis, diagnosis of PCP was independently adjudicated by 2 study investigators after reviewing reports from study sites.A total of 252 persons had a β-glucan result that could be analyzed, 173 (69%) of whom had received a diagnosis of PCP. Median β-glucan with PCP was 408 pg/mL (interquartile range [IQR], 209-500 pg/mL), compared with 37 pg/mL (IQR, 31-235 pg/mL) without PCP (P < .001). The sensitivity of β-glucan dichotomized at 80 pg/mL for the diagnosis of PCP was 92% (95% confidence interval [CI], 87%-96%), and the specificity was 65% (95% CI, 53%-75%); positive and negative predictive values were 85% (95% CI, 79%-90%) and 80% (95% CI, 68%-89%) respectively, based on the study prevalence of 69% of patients with PCP. Rates of abnormal lactate dehyrogenase levels did not differ significantly between those with and without PCP.Blood (1 → 3)-β-D-glucan is strongly correlated with HIV-related PCP. In some clinical centers, this may be a more sensitive test than the induced sputum examination and could reduce the need for both bronchoscopy and empirical therapy of PCP.

    View details for DOI 10.1093/cid/cir335

    View details for Web of Science ID 000293024000014

    View details for PubMedID 21690628

  • Cost-effectiveness of antiretroviral regimens in the World Health Organization's treatment guidelines: a South African analysis AIDS Bendavid, E., Grant, P., Talbot, A., Owens, D. K., Zolopa, A. 2011; 25 (2): 211-220

    Abstract

    the World Health Organization (WHO) recently changed its first-line antiretroviral treatment guidelines in resource-limited settings. The cost-effectiveness of the new guidelines is unknown.comparative effectiveness and cost-effectiveness analysis using a model of HIV disease progression and treatment.using a simulation of HIV disease and treatment in South Africa, we compared the life expectancy, quality-adjusted life expectancy, lifetime costs, and cost-effectiveness of five initial regimens. Four are currently recommended by the WHO: tenofovir/lamivudine/efavirenz; tenofovir/lamivudine/nevirapine; zidovudine/lamivudine/efavirenz; and zidovudine/lamivudine/nevirapine. The fifth is the most common regimen in current use: stavudine/lamivudine/nevirapine. Virologic suppression and toxicities determine regimen effectiveness and cost-effectiveness.choice of first-line regimen is associated with a difference of nearly 12 months of quality-adjusted life expectancy, from 135.2 months (tenofovir/lamivudine/efavirenz) to 123.7 months (stavudine/lamivudine/nevirapine). Stavudine/lamivudine/nevirapine is more costly and less effective than zidovudine/lamivudine/nevirapine. Initiating treatment with a regimen containing tenofovir/lamivudine/nevirapine is associated with an incremental cost-effectiveness ratio of $1045 per quality-adjusted life year compared with zidovudine/lamivudine/nevirapine. Using tenofovir/lamivudine/efavirenz was associated with the highest survival, fewest opportunistic diseases, lowest rate of regimen substitution, and an incremental cost-effectiveness ratio of $5949 per quality-adjusted life year gained compared with tenofovir/lamivudine/nevirapine. Zidovudine/lamivudine/efavirenz was more costly and less effective than tenofovir/lamivudine/nevirapine. Results were sensitive to the rates of toxicities and the disutility associated with each toxicity.among the options recommended by WHO, we estimate only three should be considered under normal circumstances. Choice among those depends on available resources and willingness to pay. Stavudine/lamivudine/nevirapine is associated with the poorest quality-adjusted survival and higher costs than zidovudine/lamivudine/nevirapine.

    View details for DOI 10.1097/QAD.0b013e328340fdf8

    View details for Web of Science ID 000285501900012

    View details for PubMedID 21124202

  • Concerns Regarding a Randomized Study of the Timing of Antiretroviral Therapy in Zimbabweans with AIDS and Acute Cryptococcal Meningitis CLINICAL INFECTIOUS DISEASES Grant, P. M., Aberg, J. A., Zolopa, A. R. 2010; 51 (8): 984-985

    View details for DOI 10.1086/656435

    View details for Web of Science ID 000282036700018

    View details for PubMedID 20858075

  • Early Antiretroviral Therapy for Patients With Acute AIDS-Related Opportunistic Infections: A Cost-Effectiveness Analysis of ACTG A5164 HIV CLINICAL TRIALS Sax, P. E., Sloan, C. E., Schackman, B. R., Grant, P. M., Rong, J., Zolopa, A. R., Powderly, W., Losina, E., Freedberg, K. A. 2010; 11 (5): 248-259

    Abstract

    ACTG A5164 demonstrated that early antiretroviral therapy (ART) in HIV-infected patients with acute opportunistic infections (OIs) reduced death and AIDS progression compared to ART initiation 1 month later. We project the life expectancies, costs, and incremental cost-effectiveness ratios (ICERs) of these strategies.using an HIV simulation model, we compared 2 strategies for patients with acute OIs: (1) an intervention to deliver early ART, and (2) deferred ART. Parameters from ACTG A5164 included initial mean CD4 count (47/microL), linkage to outpatient care (87%), and immune reconstitution inflammatory syndrome 1 month after ART initiation (7%). The estimated intervention cost was $1,650/patient.early ART lowered projected 1-year mortality from 10.4% to 8.2% and increased life expectancy from 10.07 to 10.39 quality-adjusted life-years (QALYs). Lifetime costs increased from $385,220 with deferred ART to $397,500 with early ART, primarily because life expectancy increased, producing an ICER of $38,600/QALY. Results were most sensitive to increased intervention cost and decreased virologic efficacy in the early ART strategy.an intervention to initiate ART early in patients with acute OIs improves survival and meets US cost-effectiveness thresholds. Programs should be developed to implement this strategy at sites where HIV-infected patients present with OIs.

    View details for DOI 10.1310/hct1105-248

    View details for Web of Science ID 000284681400002

    View details for PubMedID 21126955

  • Optimal antiretroviral therapy: HIV-1 treatment strategies to avoid and overcome drug resistance CURRENT OPINION IN INVESTIGATIONAL DRUGS Grant, P. M., Zolopa, A. R. 2010; 11 (8): 901-910

    Abstract

    Potent antiretroviral therapy (ART) has transformed HIV infection into a chronic manageable disease, but drug resistance remains a common problem that limits the effectiveness and clinical benefits of treatment. With increasing experience with ART, the understanding of viral dynamics of HIV improved, and researchers learned how challenging HIV can be to control. With new-class and new-generation drugs, it is hoped that the lessons learned will be useful for limiting drug resistance and optimizing the use of ART for long-term management of HIV infection.

    View details for Web of Science ID 000280192200005

    View details for PubMedID 20721832

  • Risk Factor Analyses for Immune Reconstitution Inflammatory Syndrome in a Randomized Study of Early vs. Deferred ART during an Opportunistic Infection PLOS ONE Grant, P. M., Komarow, L., Andersen, J., Sereti, I., Pahwa, S., Lederman, M. M., Eron, J., Sanne, I., Powderly, W., Hogg, E., Suckow, C., Zolopa, A. 2010; 5 (7)

    Abstract

    Immune reconstitution inflammatory syndrome (IRIS) is reported widely in patients initiating antiretroviral therapy (ART). However, few studies are prospective, and no study has evaluated the impact of the timing of ART when allocated randomly during an acute opportunistic infection (OI).A5164 randomized 282 subjects with AIDS-related OIs (tuberculosis excluded), to early or deferred ART. IRIS was identified prospectively using pre-defined criteria. We evaluated associations between IRIS and baseline variables in subjects with follow-up on ART using Wilcoxon and Fisher's exact tests, logistic regression, and Cox models with time-varying covariates. Twenty of 262 (7.6%) subjects developed IRIS after a median of 33 days on ART. Subjects with fungal infections (other than pneumocystis) developed IRIS somewhat more frequently (OR = 2.7; 95% CI: 1.02, 7.2; p-value = 0.06 (using Fisher's exact test)). In Cox models, lower baseline and higher on-treatment CD4+ T-cell counts and percentage were associated with IRIS. Additionally, higher baseline and lower on-treatment HIV RNA levels were associated with IRIS. Corticosteroids during OI management and the timing of ART were not associated with the development of IRIS.In patients with advanced immunosuppression and non-tuberculous OIs, the presence of a fungal infection, lower CD4+ T-cell counts and higher HIV RNA levels at baseline, and higher CD4+ T-cell counts and lower HIV RNA levels on treatment are associated with IRIS. Early initiation of ART does not increase the incidence of IRIS, and concern about IRIS should not prompt deferral of ART.ClinicalTrials.gov NCT00055120.

    View details for DOI 10.1371/journal.pone.0011416

    View details for Web of Science ID 000279465500005

    View details for PubMedID 20617176

  • Predicting Tipranavir and Darunavir Resistance Using Genotypic, Phenotypic, and Virtual Phenotypic Resistance Patterns: an Independent Cohort Analysis of Clinical Isolates Highly Resistant to All Other Protease Inhibitors ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Talbot, A., Grant, P., Taylor, J., Baril, J., Liu, T. F., Charest, H., Brenner, B., Roger, M., Shafer, R., Cantin, R., Zolopa, A. 2010; 54 (6): 2473-2479

    Abstract

    Genotypic interpretation systems (GISs) for darunavir and tipranavir susceptibility are rarely tested by the use of independent data sets. The virtual phenotype (the phenotype determined by Virco [the "Vircotype"]) was used to interpret all genotypes in Québec, Canada, and phenotypes were determined for isolates predicted to be resistant to all protease inhibitors other than darunavir and tipranavir. We used multivariate analyses to predict relative phenotypic susceptibility to darunavir and tipranavir. We compared the performance characteristics of the Agence Nationale de Recherche sur le Sida scoring algorithm, the Stanford HIV database scoring algorithm (with separate analyses of the discrete and numerical scores), the Vircotype, and the darunavir and tipranavir manufacturers' scores for prediction of the phenotype. Of the 100 isolates whose phenotypes were determined, 89 and 72 were susceptible to darunavir and tipranavir, respectively. In multivariate analyses, the presence of I84V and V82T and the lack of L10F predicted that the isolates would be more susceptible to darunavir than tipranavir. The presence of I54L, V32I, and I47V predicted that the isolates would be more susceptible to tipranavir. All GISs except the system that provided the Stanford HIV database discrete score performed well in predicting the darunavir resistance phenotype (R(2) = 0.61 to 0.69); the R(2) value for the Stanford HIV database discrete scoring system was 0.38. Other than the system that provided the Vircotype (R(2) = 0.80), all GISs performed poorly in predicting the tipranavir resistance phenotype (R(2) = 0.00 to 0.31). In this independent cohort harboring highly protease inhibitor-resistant HIV isolates, reduced phenotypic susceptibility to darunavir and tipranavir was rare. Generally, GISs predict susceptibility to darunavir substantially better than they predict susceptibility to tipranavir.

    View details for DOI 10.1128/AAC.00096-10

    View details for Web of Science ID 000277756000025

    View details for PubMedID 20368406

  • International Cohort Analysis of the Antiviral Activities of Zidovudine and Tenofovir in the Presence of the K65R Mutation in Reverse Transcriptase ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Grant, P. M., Taylor, J., Nevins, A. B., Calvez, V., Marcelin, A., Wirden, M., Zolopa, A. R. 2010; 54 (4): 1520-1525

    Abstract

    A K65R mutation in HIV-1 reverse transcriptase can occur with the failure of tenofovir-, didanosine-, abacavir-, and, in some cases, stavudine-containing regimens and leads to reduced phenotypic susceptibility to these drugs and hypersusceptibility to zidovudine, but its clinical impact is poorly described. We identified isolates with the K65R mutation within the Stanford Resistance Database and a French cohort for which subsequent treatment and virological response data were available. The partial genotypic susceptibility score (pGSS) was defined as the genotypic susceptibility score (GSS) excluding the salvage regimen's nucleoside reverse transcriptase inhibitor (NRTI) component. A three-part virologic response variable was defined (e.g., complete virologic response, partial virologic response, and no virologic response). Univariate, multivariate, and bootstrap analyses evaluated factors associated with the virologic response, focusing on the contributions of zidovudine and tenofovir. Seventy-one of 130 patients (55%) achieved a complete virologic response (defined as an HIV RNA level of <200 copies/ml). In univariate analyses, pGSS and zidovudine use in the salvage regimen were predictors of the virologic response. In a multivariate analysis, pGSS and zidovudine and tenofovir use were associated with the virologic response. Bootstrap analyses showed similar reductions in HIV RNA levels with zidovudine or tenofovir use (0.5 to 0.9 log(10)). In the presence of K65R, zidovudine and tenofovir are associated with similar reductions in HIV RNA levels. Given its tolerability, tenofovir may be the preferred agent over zidovudine even in the presence of the K65R mutation.

    View details for DOI 10.1128/AAC.01380-09

    View details for Web of Science ID 000275662700017

    View details for PubMedID 20124005

  • Switch from enfuvirtide to raltegravir in virologically suppressed HIV-1 infected patients: Effects on level of residual viremia and quality of life JOURNAL OF CLINICAL VIROLOGY Grant, P. M., Palmer, S., Bendavid, E., Talbot, A., Slamowitz, D. C., Cain, P., Kobayashi, S. S., Balamane, M., Zolopa, A. R. 2009; 46 (4): 305-308

    Abstract

    Raltegravir is a potential treatment option for virologically suppressed HIV-1 infected patients on enfuvirtide with injection site reactions.To characterize safety and efficacy of an enfuvirtide to raltegravir switch including changes in T-cells, quality of life, and residual viremia.In patients with viral load <50 copies/mL and injection site reactions, enfuvirtide was switched to raltegravir without additional changes to the antiretroviral regimen. Virologic failure was defined as a viral load >1000 copies/mL or two consecutive viral load measurements between 50 and 1000 copies/mL (low-level viremia). Over the 24 week study, we compared changes in T-cells, injection site reactions, quality of life, and residual viremia, as measured through the single-copy assay which can detect plasma virus down to a single copy, using paired t-tests.Fourteen patients with a median CD4+ T-cell count of 420 cells/microL were enrolled. After the switch, two patients experienced virologic failure due to confirmed low-level viremia. However, both patients subsequently were re-suppressed, one without any changes to his regimen. There was no change in CD4+ T-cell count. Injection site reactions resolved. However, there was little reported change in quality of life. The baseline median level of residual viremia was 6 copies/mL and did not change after the switch to raltegravir.A switch to raltegravir in virologically suppressed patients on enfuvirtide is effective in maintaining immunologic and virologic control at 24 weeks but did not result in a change in residual viremia.

    View details for DOI 10.1016/j.jcv.2009.09.025

    View details for Web of Science ID 000272460900002

    View details for PubMedID 19819183

  • The use of resistance testing in the management of HIV-1-infected patients CURRENT OPINION IN HIV AND AIDS Grant, P. M., Zolopa, A. R. 2009; 4 (6): 474-480

    Abstract

    Resistance testing has become an important component of the recommended care for treatment-naive and treatment-experienced HIV-infected patients in the developed world, and their use has been shown to improve clinical outcomes. Despite the widespread use of resistance testing, the clinician faces a number of challenges in optimally applying these technologies to antiretroviral management.Even with the aid of a genotypic interpretation system, the interpretation of a genotype is complex and benefits from expert input. Phenotypic resistance testing is limited by cost and availability for many patients. Standard resistance testing (both genotypes and phenotypes) is unable to detect minority species. The presence of resistant minority populations has been associated with virologic failure. However, the current techniques available to detect their presence are cumbersome and not soon likely to become part of routine clinical care. The development of the chemokine (C-C motif) receptor 5 antagonists has provided new challenges in quantifying antiretroviral resistance.Resistance testing plays a central role in the management of treatment-experienced patients. Further progress in the interpretation of resistance testing, especially as new agents are developed, will continue to add value to the care of HIV-infected patients.

    View details for DOI 10.1097/COH.0b013e328331c14f

    View details for Web of Science ID 000208083400003

    View details for PubMedID 20048713

  • Initiation of antiretroviral therapy in the hospitalized patient with an acute AIDS-related opportunistic infection and other conditions: no time to lose. Current HIV/AIDS reports Grant, P., Zolopa, A. 2009; 6 (2): 63-67

    Abstract

    Treatment guidelines have recently become more definitive regarding the optimal timing for initiation of combination antiretroviral therapy (ART) in the setting of an acute AIDS-related opportunistic infection (OI). These recent changes reflect new data from a prospective, randomized study and several retrospective studies, all of which support earlier initiation of ART during an OI. These studies focus on OIs for which effective antimicrobial therapy exists. For AIDS-related conditions that lack effective antimicrobial therapy, there are few studies to help inform the optimal timing to initiate ART, but most clinicians initiate ART early, as little else can be offered to these patients. For patients with HIV admitted for non-AIDS-related conditions, there are few data that directly address the optimal timing for ART. Initiating ART in the hospitalized patient can be challenging and requires a well-coordinated multidisciplinary team with expertise in ART management.

    View details for PubMedID 19358776

  • Maintaining Reduced Viral Fitness and CD4 Response in HIV-Infected Patients with Viremia Receiving a Boosted Protease Inhibitor CLINICAL INFECTIOUS DISEASES Grant, P., Taylor, J., Cain, P., Short, W., Gallant, J., Farthing, C., Thal, G., Coakley, E., Zolopa, A. 2009; 48 (5): 680-682

    Abstract

    When fully suppressive regimens are not available, incompletely suppressive regimens also provide immunologic benefits. In this study, with stable background therapy, human immunodeficiency virus (HIV)-infected patients who were randomized to receive atazanavir or boosted atazanavir, compared with those who continued boosted protease inhibitor therapy, maintained similar virologic and immunologic control, resistance-mutation patterns, and replication capacities with reduced use of lipid-lowering medication.

    View details for DOI 10.1086/597008

    View details for Web of Science ID 000263061700026

    View details for PubMedID 19191657

  • Virologic Response to Lopinavir-Ritonavir-Based Antiretroviral Regimens in a Multicenter International Clinical Cohort: Comparison of Genotypic Interpretation Scores ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Grant, P., Wong, E. C., Rode, R., Shafer, R., De Luca, A., Nadler, J., Hawkins, T., Cohen, C., Harrington, R., Kempf, D., Zolopa, A. 2008; 52 (11): 4050-4056

    Abstract

    Several genotypic interpretation scores have been proposed for the evaluation of susceptibility to lopinavir/ritonavir (LPV/r) but have not been compared using an independent data set. This study was a retrospective multicenter cohort of patients initiating LPV/r-based therapy. The virologic response (VR) was defined as a viral load of <500 copies/ml at week 24. The genotypic interpretation scores surveyed were the LPV mutation score, the ViroLogic score, the ATU score, the Stanford database score, and the International AIDS Society-USA mutation list. Of the 103 patients included in the analysis, 76% achieved VR at 24 weeks. For scores with clinical breakpoints defined (LPV mutation, ATU, ViroLogic, and Stanford), over 80% of the patients below the breakpoints achieved VR, while 50% or less above the breakpoints responded. Protease mutations at positions 10, 54, and 82 and at positions 54, 84, and 90 were associated with a lack of VR in the univariate and multivariate analyses, respectively. The area under the receiver-operator characteristic curves for the five genotypic interpretation scores studied ranged from 0.73 to 0.76. The study confirms that the currently available genotypic interpretation scores which are widely used by clinicians performed similarly well and can be effectively used to predict the virologic activity of LPV/r in treatment-experienced patients.

    View details for DOI 10.1128/AAC.00605-08

    View details for Web of Science ID 000260305600032

    View details for PubMedID 18710915

  • Integrase inhibitors: a clinical review of raltegravir and elvitegravir. Journal of HIV therapy Grant, P., Zolopa, A. 2008; 13 (2): 36-39

    View details for PubMedID 18953272

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