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Antiretroviral Treatment Highlights of the 11th Conference on Retroviruses and Opportunistic Infections (CROI) February 8-11, 2004; San Francisco, California. Selected and summarized by Jeffrey P. Nadler, MD, FACP USF College of Medicine Tampa, Florida.

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Selected and summarized by jeffrey p nadler md facp usf college of medicine tampa florida l.jpg

Antiretroviral Treatment Highlights of the 11th Conference on Retroviruses and Opportunistic Infections (CROI)February 8-11, 2004; San Francisco, California

Selected and summarized byJeffrey P. Nadler, MD, FACP

USF College of Medicine

Tampa, Florida

Supported by an unrestricted educational grant from


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Antiretroviral Treatment Highlights of the 11th Conference on Retroviruses and Opportunistic Infections

New Data On:

  • Initial antiretroviral therapy

  • Treatment failure and second-line therapy

  • New and investigational agents

  • Complications of HIV infection and its therapy


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Initial Antiretroviral Therapy (1) on Retroviruses and Opportunistic InfectionsLopinavir/Ritonavir (LPV/RTV) Once Daily (QD) vs Twice Daily (BID):48-Week Data

  • LPV/RTV 800/200 mg QD+ QD emtricitabine/tenofovir DF (n = 115)

  • LPV/RTV 400/100 mg BID+ QD emtricitabine/tenofovir DF(n = 75)

  • Efficacy

    • Patients with HIV-1 RNA < 50 copies/mL (ITT): 70% vs 64%

    • Mean increase in CD4+ cell count (cells/mcL): 185 vs 188

  • Prospective, randomized, comparative study of 2 initial antiretroviral regimens

    • Adverse Events/Lipid Effects

      • Moderate-to-severe diarrhea: 16%vs 4%(P = .04)

      • Resulted in discontinuation of treatment: 12%vs 5%

      • Lipid elevations were common, but equivalent in study arms

    • Similar virologic and immunologic responses with QD andBID regimens; more adverse GI effects in QD arm

    Abstract 570


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    Initial Antiretroviral Therapy (2) on Retroviruses and Opportunistic InfectionsOnce-Daily (QD) Didanosine (ddI) + Lamivudine (3TC) + Tenofovir DF (TDF)

    • 22 treatment-naive patients enrolled

    • 20 discontinued prematurely due to early virologic failure

  • Patients with resistance-associated mutations post-therapy (n = 20)

    • M184V/I: 20 (100%)

    • K65R: 10 (50%); 7 mixed with wild-type

  • Decrease in HIV-1 RNA at week 24

    • 0.49 log10 copies/mL (median), despite absence of phenotypic TDF resistance

  • QD ddI+3TC+TDFproduced suboptimal responses and rapid emergence of resistance-associated mutations

  • 24-week pilot study evaluating potency and safety of ddI+3TC+TDF

    Abstract 51


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    Initial Antiretroviral Therapy (3) on Retroviruses and Opportunistic InfectionsOnce-Daily (QD) Abacavir (ABC) + Lamivudine (3TC) + Tenofovir (TDF): Tonus Study

    • Efficacy

      • Virologic failures (any timepoint):12/36

        • 4 patients had early viral rebound > 0.7 log10 copies/mL

        • 8 patients never achieved HIV-1 RNA < 400 copies/mL

      • Virologic responders (HIV-1 RNA < 50 copies/mL at 24 weeks): 17/26

        • All (8) patients who entered study with HIV-1 RNA < 10,000 copies/mL

        • 9 of 18 patients with baseline HIV-1 RNA > 10,000 copies/mL

    • High rate of early virologic failure similar to those observed in other recent studies of ABC+3TC+TDF

    Pilot study of 38 antiretroviral-naive patients treated with QD ABC+3TC+TDF

    Abstract 52


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    Initial Antiretroviral Therapy (3) Continued on Retroviruses and Opportunistic InfectionsOnce-Daily (QD) Abacavir (ABC) + Lamivudine (3TC) + Tenofovir (TDF): Tonus Study

    • Rapid selection of resistance-associated mutations

      • Virologic failure: HIV RT mutations in patients with virologic failure at 3-6 months (n = 12)

        • M184V + K65R: 11/12

        • M184Vonly: 1/12

      • No virologic failure: HIV RT mutations in patients with HIV-1 RNA < 400 copies/mL (n = 10)

        • M184V + K65R: 7/10

        • M184Vonly: 2/10

    • Plasma and intracellular drug levels

      • adequate plasma trough concentrations (Cmin), all drugs (week 4): 32/37

      • detectable intracellular metabolites, all drugs: 8/14

    • Results support a low genetic barrier to resistance as the major cause of virologic failure

    Abstract 52


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    Initial Antiretroviral Therapy (4) on Retroviruses and Opportunistic InfectionsOnce-Daily (QD) Trizivir (TZV) + Tenofovir DF (TDF): COL40263

    Early, interim analysis of a pilot study of QD quadruple-NRTI/NtRTI regimen in antiretroviral-naive subjects

    • 54/88 completed > 24 weeks’ follow-up at interim analysis

    • Median baseline HIV-1 RNA: 5.1 log10 copies/mL (52% ≥ 100,000 copies/mL)

    • Median baseline CD4+ cell count: 226 cells/mcL (37% < 200 cells/mcL)

  • Efficacy (24 weeks)

    • HIV genotypes in nonresponders: 2 WT, 1 K65R, 3 M184V + TAMS, 2 TAMS

  • Although preliminary, once-daily TZV+TDF may prove useful in patients with lower viral loads

  • Abstract 53


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    Treatment Failure and Second-line Therapy (1) on Retroviruses and Opportunistic InfectionsAtazanavir (ATV)/Ritonavir (RTV) vs ATV/Saquinavir (SQV) vs Lopinavir (LPV)/RTV: BMS 045 (48-Week Results)

    • Patients randomized to receive:

      • ATV/RTV QD+ tenofovir DF + 1 NRTI (n = 120 )

      • ATV/SQV QD+ tenofovir DF + 1 NRTI (n = 115 )

      • LPV/RTV BID+ tenofovir DF + 1 NRTI (n = 123 )

  • Efficacy

  • Overall,ATV/RTV was comparable in efficacy toLPV/RTV

  • Ongoing, prospective study in patients with ≥ 2 prior HAART failures

    Abstract 547


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    Treatment Failure and Second-line Therapy (1) Continued on Retroviruses and Opportunistic InfectionsAtazanavir (ATV)/Ritonavir (RTV) vs ATV/Saquinavir (SQV) vs Lopinavir (LPV)/RTV: BMS 045 (48-Week Results)

    • Lipid effects (mean % change from baseline at week 48)

    • ATV regimens were generally associated with favorable lipid effects compared with LPV/RTV

    • Safety

      • Frequency of adverse events and discontinuations was similar across treatment arms

        • ATV/RTV wasassociated with hyperbilirubinemia (and some cases of jaundice)

        • Diarrhea was observed to occur with greater frequency in the LPV/RTVarm

    HDL-C = high-density lipoprotein cholesterol; LDC-C = low-density lipoprotein cholesterol.

    *P< .005 (ATV regimens vs LPV/RTV)

    Abstract 547


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    New and Investigational Agents (1) on Retroviruses and Opportunistic InfectionsBinding/Fusion Inhibitors


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    New and Investigational Agents (2) on Retroviruses and Opportunistic InfectionsBinding/Fusion Inhibitors


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    New and Investigational Agents (3) on Retroviruses and Opportunistic InfectionsNucleoside/Nucleotide Analogs


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    New and Investigational Agents (4) on Retroviruses and Opportunistic InfectionsAdditional Developmental Agents


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    Complications of HIV Infection and Its Therapy (1) on Retroviruses and Opportunistic InfectionsHyperglycemia and Diabetes

    • This cohort study shows increased incidence and prevalence in prediabetes and diabetes in HIV-infected men exposed to HAART

    Prevalence of hyperglycemia examined in cohort of men enrolled in the Multicenter AIDS Cohort Study (MACS)

    • Analysis

      • data on 1107 men from April 1999 – September 2002

        • 563 HIV-negative, 544 HIV-infected, 423 on HAART

    • Results

      • HIV-infected men on HAART had a 5-fold increased likelihood of hyperglycemia or diabetes

      • Incident risk was 2-fold compared with HIV-negative men

      • 1.8-fold risk increase with HIV infection alone, 3.1-fold with HAART

    • Drugs associated with increased risk (hazard ratio [95% CI])

      • Protease inhibitors (1.9 [1.1-1.3]), stavudine (2.1 [1.1- 3.9]), and efavirenz (3.9 [1.6-9.5])

    Abstract 73


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    Complications of HIV Infection and Its Therapy (2) on Retroviruses and Opportunistic InfectionsPredictors of Hypertension in HIV-Infected Patients in the D:A:D Study

    • Longitudinal assessment of potential patient- and treatment-related factors associated with differences in blood pressure (BP) and hypertension among HIV-infected adults

    • Results

      • 487 of 8341 patients with normal baseline BP developed hypertension

        • Incidence = 35.8/1000 person-years

      • Factors associated with increased risk for hypertension included the usual suspects: older age, male sex, higher body mass index, and higher baseline BP measurements

    • Predictors of hypertension subsequent to enrollment in the D:A:D cohort were assessed for 16,002 patients followed for a median of 1.5 years (range, 0.8-1.7)

    • 8341patients with normal BP at baseline were included in the primary analysis

    • Antiretroviral therapy was not a predictor of hypertension

      • By cumulative duration of exposure to each class of antiretroviral

      • By type of regimen at baseline

    • Antiretroviral therapy was not an independent prognostic factor of blood pressure changes or hypertension in this study

    Abstract 75


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    Complications of HIV Infection and Its Therapy (3) on Retroviruses and Opportunistic InfectionsRosiglitazone (RSG) Therapy for Lipoatrophy

    • Double-blind, placebo-controlled 48-week trial of 108 HIV+ patients with lipoatrophy

    • Key findings (48 weeks; ITT)

      • RSG had no effect on mean limb fat changes (vs placebo): 0.14 kg vs 0.18 kg

        • No differences according to PI or thymidine analog use

    • Lipoatrophic patients (limb fat mass < 20%) randomized to

      • RSG 4 mg bid (max dose) (n = 53) or placebo(n = 55)

    • All patients were on stable antiretroviral therapy (≥ 3 months) including a PI and/or thymidine analog (zidovudine or stavudine)

    • RSG associated with significant adverse lipid effects

      • Mean increase in total cholesterol: 16% vs 0% (P = .0001)

      • Mean increase in triglycerides: 40% vs 7% (P = .007)

    • RSG associated with improvements in insulin sensitivity

    • Rosiglitazone not effective for the treatment of HIV/antiretroviral therapy-associated lipoatrophy

    Abstract 79


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    Complications of HIV Infection and Its Therapy (4) on Retroviruses and Opportunistic InfectionsEffects of Switching PI to NNRTI or Abacavir to Treat Lipodystrophy:NEFA Substudy

    • Metabolic outcomes at 24 months (% change from baseline)

    • Analysis from a randomized study of patients who substituted abacavir (ABC), efavirenz (EFV), or nevirapine (NVP) for PI

    LDL-C = low-density lipoprotein cholesterol; TC:HDL-C = Total cholesterol:high-density lipoprotein cholesterol ratio

    • Switch to any of the 3 treatments improved insulin resistance, total cholesterol (TC), LDL-C, and TC:HDL-C ratio

    • Slightly better changes in TC:HDL-C were seen with switch to either NNRTI vs ABC

    • Marked metabolic improvements were seen with switch to PI-sparing therapy

    Abstract 78


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