NORTHWEST AIDS EDUCATION AND TRAINING CENTER

2012 HIV Update
David Spach, MD Clinical Director, Northwest AETC Professor of Medicine, Division of Infectious Diseases University of Washington
Presentation Prepared by: David Spach, MD Last Updated: April 16, 2012

2012 HIV Clinical Update: Topics
 Acute (Primary) HIV Infection  2012 HHS Antiretroviral Therapy Guidelines  Recognizing Common Clinical Manifestations

 Healthcare Postexposure Prophylaxis

HIV 2012 UPDATE

Acute HIV

In addition. and fatigue. myalgias. for one day he has a diffuse maculopapular. . He had anonymous sex with 2 men about 3 weeks ago. sore throat. erythematous rash.A 22-Year-Old Man with a Flu-Like Illness • A 22-year-old man is seen in the urgent care clinic with a 3day history of fever. headache.

Morbilliform Rash Photograph from David Spach. MD .

A 22-Year-Old Man with a Flu-Like Illness • What is in your differential diagnosis? • What tests would you order? .

et al. 2000.PRIMARY (ACUTE) HIV Clinical Manifestations of Primary HIV Infection Fever Lethargy Myalgias Rash Headache Pharyngitis Adenopathy 0 10 20 30 40 86 74 59 57 55 52 44 50 60 70 80 90 100 N =160 Patients % From: Vanhems P. AIDS. .14:375-81.

Acute (Primary) HIV: Eclipse Phase
Eclipse Phase 10,000,000

HIV RNA (copies/ml)

1,000,000 100,000 10,000 1,000

100
10 1 0 5 10 15 20

HIV RNA Limit of Detection

25

30

35

40

45

50

Days following HIV Acquisition
Eclipse Phase = Time between infection and detectable HIV RNA

Acute (Primary) HIV: Window Period
Window Period

Antibody Titer
0

5

10

15

20

25

30

35

40

45

50

Days following HIV Acquisition
Window Period = Time between infection and detectable HIV antibodies

PRIMARY (ACUTE) HIV

Acute (Primary) HIV: Symptomatic Disease
Acute Illness 10,000,000 30

HIV RNA (copies/ml)

1,000,000

10,000 20 1,000

100
10 1 0 5 10 15 20 25 30 35 40 45 50

15

10

Days following HIV Tansmission
Symptomatic Disease Often Precedes Positive Antibody Test

Antibody Titer

100,000

25

Transmission of HIV HIV + - .

Transmission of HIV Chronic HIV infection Quasispecies HIV-Negative + - .

Transmission of HIV: Founder Virus Chronic HIV infection Quasispecies New Infected with HIV Founder Virus + + .

Acute (Primary) HIV High Transmission Risk + .

Acute (Primary) HIV Factors Associated with High Transmission Risk • • • • Unaware of HIV status High “viral load” Homogeneity of transmission-capable viral variants Low titer of neutralizing antibodies - - - + - .

HIV 2012 UPDATE HHS Antiretroviral Therapy Recommendations .

nih.aidsinfo. AIDS Info (www.US Health and Human Services (HHS) March 27. 2012 Antiretroviral Therapy Guidelines Source: 2012 HHS Antiretroviral Therapy Guidelines.gov) .

or substance abuse issues. 710. His CD4 counts have been 770. He has no active medical. 640. She is seen in the clinic for follow up. He is sexually active with other men and uses condoms most of the time.Case History • A 28-year-old man was diagnosed with HIV about 18 months ago. • Would you recommend starting antiretroviral therapy? . mental health. and 610 cells/mm3.

AIDS Info (www.aidsinfo.gov) .nih.ANTIRETROVIRAL THERAPY: HHS GUIDELINES HHS Antiretroviral Therapy Guidelines: March 2012 Initiating Therapy in Treatment-Naïve Patients 1000 CD4 Cell Count 800 Recommend: Moderate (BIII) 600 500 400 Recommend: Strong (AII) 350 200 Recommend: Strong (AII) 0 Source: 2012 HHS Antiretroviral Therapy Guidelines.

ANTIRETROVIRAL THERAPY: HHS GUIDELINES Initiating Antiretroviral Therapy in Treatment-Naïve Patients Change in CD4 Threshold in HHS Guidelines 1000 CD4 Cell Count 800 2012 600 500 400 2009 2007 350 200 200 2003 0 .

ANTIRETROVIRAL THERAPY: HHS GUIDELINES HHS Antiretroviral Therapy Guidelines: March 2012 Initiating Therapy in Treatment-Naïve Patients Earlier Therapy Later Therapy .

Initiating Antiretroviral Therapy Why are we treating earlier with antiretroviral therapy? .

ANTIRETROVIRAL THERAPY: HHS GUIDELINES HHS Antiretroviral Therapy Guidelines: March 2012 Factors Affecting Decision on When to Initiate Therapy • More effective regimens • More convenient regimens • Better tolerated therapy • Less long-term toxicity • Better immune recovery • Lower rates of resistance • More treatment options • Concerns for uncontrolled viremia • Decrease HIV transmission • Lack of RCT data supporting early Rx • Potential drug toxicity • Drug and monitoring cost • Potential negative impact on QOL .

PREVENTION OF OPPORTUNISTIC INFECTIONS CD4 Cell Progression (without Antiretroviral Therapy) 1000 800 600 CD4 Cell Count 400 200 AIDS 0 0 Year 1 1 2 3 4 5 6 Years 7 8 9 10 11 12 13 14 15 .

Chronic Immune Activation and Inflammation 1000 800 600 CD4 Cell Count Immune Activation & Inflammation 400 200 0 0 1 0 0 Year 0 0 (expanded) 1 2 3 4 5 6 Years 7 8 9 10 11 12 13 14 15 .

0 0. et al. .00 1.0 1.5 1. 2010.58 1.5 0.29 CD4 ≥500 cells/µl CD4 350-499 cells/µl CD4 <350 cells/µl Baseline CD4 Cell Count Source: Lichtenstein KA.5 2. Clin Infect Dis.0 Hazard Ratio N = 2. January 2002–September 2009 Cox Proportional Hazards: Relationship of Baseline CD4 and Risk of Subsequent Cardiovascular Events 2.51:435-47.ANTIRETROVIRAL THERAPY Attributable Risk Factors Associated with Cardiovascular Disease Events HOPS Study.005 1.

5 25.4 13. .51:435-47.3 20. January 2002–September 2009 Baseline Factor Associated with Incident Cardiovascular Disease Events Diabetes Male gender HDL < 40 male HLD < 50 female LDL/nonHDL > goal CD4 < 500 cells/µl Tobacco Smoking Hypertension Age ≥42 years (median) 2. 2010.2 0 10 20 30 40 50 60 Attributable Risk (%) Source: Lichtenstein KA. Clin Infect Dis.ANTIRETROVIRAL THERAPY: DHHS GUIDELINES Attributable Risk Factors Associated with Cardiovascular Disease Events HOPS Study.7 34.9 21.6 26.4 N = 2.005 49. et al.

Chronic Inflammation Impact on HIV-Infected Persons • Increased risk of heart disease • Increased risk of stroke • Increased risk of cancer .

763 HIV Serodiscordant Couples (97% heterosexual) + - + - + - + - n = 872 n = 853 n = 37 n=1 Source: Cohen M. et al.HIV Prevention Trials Network (HPTN) Study 052 1. 2011. N Engl J Med.36:493-505. .

N Engl J Med. 2011.ANTIRETROVIRAL THERAPY: DHHS GUIDELINES HIV Prevention Trials Network (HPTN) Study 052 1000 CD4 Cell Count 800 600 550 Early Therapy 400 CD4 350-550 cells/mm3 350 Deferred Therapy CD4 < 250 cells/mm3 or AIDS Related Event 250 200 0 Source: Cohen M. .36:493-505. et al.

. et al.001 Deferred Therapy (n = 877) 27 0 5 10 15 20 25 30 Linked Transmissions Source: Cohen M.HIV Prevention Trials Network (HPTN) Study 052 96% Reduction Early Therapy (n = 886) 1 P < 0. 2011. N Engl J Med.36:493-505.

aidsinfo. AIDS Info (www.gov) .DHHS Antiretroviral Therapy Guidelines: October 2011 Preferred Regimens for ARV-Naïve Patients: Pill Burden Class Therapy Pill Burden NNRTI-Based Efavirenz-Tenofovir-Emtricitabine Ritonavir + Atazanavir + Tenofovir-Emtricitabine PI-Based Darunavir + Ritonavir + Tenofovir-Emtricitabine INSTI-Based Raltegravir + Tenofovir-Emtricitabine Source: 2011 DHHS Antiretroviral Therapy Guidelines.nih.

gov) .aidsinfo. AIDS Info (www.nih.ANTIRETROVIRAL THERAPY: HHS GUIDELINES HHS Antiretroviral Therapy Guidelines: March 2012 Preferred Regimens for ARV-Naïve Patients: Pill Burden Class Therapy *AWP (Monthly) $2081 NNRTI-Based Efavirenz-Tenofovir-Emtricitabine Ritonavir + Atazanavir + Tenofovir-Emtricitabine PI-Based Darunavir + Ritonavir + Tenofovir-Emtricitabine $2860 $2925 INSTI-Based Raltegravir + Tenofovir-Emtricitabine $2562 *AWP = average wholesale price Source: 2012 HHS Antiretroviral Therapy Guidelines.

2011: New FDA-Approved HIV Medications (or New Preparations of Older Medications) • Nevirapine XR (Viramune XR): 400 mg tablet • Etravirine (Intelence): 200 mg tablet • Rilpivirine (Edurant): 25 mg tablet • Tenofovir-Emtricitabine-Rilpivirine (Complera): 1 pill qd .

A baseline genotype shows no mutations. She has no other medical problems.Case History • A 30-year-old woman with asymptomatic HIV infection is seen for follow-up in the clinic to discuss starting antiretroviral therapy. • Most recent labs show a CD4 cell count of 375 cells/mm3 and CD4% = 16. • Which one pill once a day regimen to give her? . She states she really wants to take the the “one pill a day” regimen.300 copies/ml. Most recent HIV RNA is 65.

Atripla versus Complera Atripla Complera Tenofovir-Emtricitabine-Efavirenz NRTI NRTI NNRTI Tenofovir-Emtricitabine-Rilpivirine NRTI NRTI NNRTI Image Source: AIDS Info.org .

Phase 3 .N = 690 (ECHO) and 678 (THRIVE) .Randomized to one of 2 arms . .Age > 18 .HIV RNA > 5.ARV-naïve .Rilpivirine vs. Efavirenz in ARV-Naive ECHO and THRIVE Pooled Data: Study Design Study Features Protocol . et al.No baseline NNRTI mutations . double-blind trial . JAIDS. Abacavir + Lamivudine Source: Cohen C.000 copies/ml .All given 2 NRTIs* Rilpivirine: 25 mg qd + TDF/FTC (n = 346) ECHO 1x Efavirenz: 600 mg qd + TDF/FTC (n = 344) Rilpivirine: 25 mg qd + 2NRTIs (n = 340) THRIVE 1x Efavirenz: 600 mg qd + 2NRTIs (n = 338) *2 NRTIs: ECHO: Tenofovir + Emtricitabine (TDF/FTC) THRIVE: Tenofovir + Emtricitabine. Zidovudine + Lamivudine. 2012:Feb 16 [Epub ahead of print].Randomized.

2012:Feb 16 [Epub ahead of print]. JAIDS. et al. . Efavirenz in ARV-Naive ECHO and THRIVE Pooled Data: Week 48 Results Virologic Response ( ITT-TLOVR) over 48 Weeks 100 Patients with Virologic Response 80 2NRTIs+ Rilpivirine (n = 686) 84% 82% 2NRTIs+ Efavirenz (n = 682) 60 40 20 0 0 2 4 8 12 16 24 32 40 48 Time (weeks) Source: Cohen C.Rilpivirine vs.

2012. et al.Rilpivirine vs.59:39-46. JAIDS. . Efavirenz in ARV-Naive ECHO and THRIVE: Virologic Failure Results Virologic Failure 48 Week Data 20 Virologic Failure 15 10 5 0 Rilpivirine: 25 mg Efavirenz: 600 mg 17 10 6 7 5 5 All ≤ 100K > 100K Baseline HIV RNA Level (copies/ml) All regimens included 2 NRTIs Source: Rimsky L.

2012 HIV UPDATE Recognizing Clinical Manifestations .

Cutaneous Manifestations .

CLINICAL MANIFESTATIONS Case History .

CLINICAL MANIFESTATIONS Case History .

CLINICAL MANIFESTATIONS Case History .

CLINICAL MANIFESTATIONS Case History .

CLINICAL MANIFESTATIONS Case History .

CLINICAL MANIFESTATIONS Case History .

CLINICAL MANIFESTATIONS Case History .

CLINICAL MANIFESTATIONS Case History .

Oral Manifestations .

CLINICAL MANIFESTATIONS Case History .

OPPORTUNISTIC INFECTIONS Case History .

CLINICAL MANIFESTATIONS Case History .

CLINICAL MANIFESTATIONS Case History .

CLINICAL MANIFESTATIONS Case History .

HIV 2012 UPDATE Postexposure Prophylaxis .

No antiretroviral postexposure prophylaxis given .Needlestick involved venipuncture needle .Skin on hand punctured .Question • What is the risk of acquiring HIV from a needlestick injury when all following are present: .HIV-infected source patient not on antiretroviral therapy .

Estimated Risk of Seroconversion with Percutaneous Injury 60 50 40 30 30 20 10 50 Seroconversion (%) 0. 2001.3 HIV 2 Hepatitis C HBsAg+ HBeAg- 0 HBsAg+ HBeAg- Source: CDC and Prevention.50(RR-11):1-42. MMWR Morb Mortal Weekly Rep. .

000 copies/ml. The nurse is immune to hepatitis B. The source patient has never been on antiretroviral therapy and has a HIV RNA level of 96. Basic Regimen (2-drugs) C. No antiretroviral therapy B. what PEP would you recommend for this nurse? A. The source patient is HIV-positive and HCV-negative. Expanded (≥3-drugs) .Case History HIV Exposure in a Health Care Worker • A 29-year-old nurse sticks herself in the finger with a needle when drawing blood from a patient. In addition to washing the wound.

1997.19 Source: Cardo DM.2 5. et al. N Engl J Med.Logistic-Regression Analysis of Risk Factors for HIV Transmission after Percutaneous Exposure to HIV-Infected Blood Risk Factors for HIV Seroconversion in Health Care Workers Risk Factor Deep Injury Visible Blood on Device Terminal Illness in Source Patient Needle in Source Vein/Artery PEP with Zidovudine (AZT) Adjusted Odds Ratio 15.0 6.6 4. .3 0.337:1485-90.

g.g.. visible blood on device.500 copies/mL) ^HIV+ Class 2: Symptomatic HIV. or known high viral load Source: CDC and Prevention. deep puncture. <1. or needle used in patient’s artery or vein *HV+ Class 1: Asymptomatic HIV infection or low viral load (e.Recommended HIV PEP after Percutaneous Exposure Known Source HIV Status Percutaneous Exposure Type Source Infection Status HIV+ Class 1* Recommend Basic 2-drug PEP Recommend Expanded 3-drug PEP HIV+ Class 2^ Recommend Expanded > 3-drug PEP Recommend Expanded > 3-drug PEP Less Severe ¶ More Severe# ¶ Less Severe: e. . 2005. solid needle or superficial injury # More Severe: e... AIDS.54(RR-9):1-17. large-bore hollow needle. MMWR Morb Mortal Weekly Rep.g. acute seroconversion.

2005. acute seroconversion..g..Recommended HIV PEP after Percutaneous Exposure Known Source HIV Status Percutaneous Exposure Type Source Infection Status HIV+ Class 1* Recommend Basic 2-drug PEP Recommend Expanded 3-drug PEP HIV+ Class 2^ Recommend Expanded > 3-drug PEP Recommend Expanded > 3-drug PEP Less Severe ¶ More Severe# ¶ Less Severe: e. MMWR Morb Mortal Weekly Rep. <1.g. large-bore hollow needle. or known high viral load Source: CDC and Prevention. AIDS.54(RR-9):1-17. . or needle used in patient’s artery or vein *HV+ Class 1: Asymptomatic HIV infection or low viral load (e. deep puncture.500 copies/mL) ^HIV+ Class 2: Symptomatic HIV. solid needle or superficial injury # More Severe: e. visible blood on device..g.

aidsinfo.ANTIRETROVIRAL THERAPY: DHHS GUIDELINES 2005 Recommended PEP Antiretroviral Therapy Preferred Basic and Expanded Regimens Drugs for Basic Regimens (28 days) Preferred Regimens Zidovudine-Lamivudine (Combivir) Lopinavir-Ritonavir (Kaletra) Tenofovir + Emtricitabine (Truvada) Alternative Regimens Stavudine (Zerit) + Lamivudine (Epivir) Atazanavir (Reyataz) + Ritonavir (Norvir) Drugs for Expanded Regimen (28 days) Basic Regimen Plus: Stavudine (Zerit) + Emtricitabine (Emtriva) Didanosine (Videx) + Lamivudine (Epivir) Didanosine (Videx) + Emtricitabine(Emtriva) Fosamprenavir (Lexiva) + Ritonavir (Norvir) Saquinavir (Invirase) + Ritonavir (Norvir) Nelfinavir (Viracept) Efavirenz (Viracept) Source: AIDS Info (www.gov) .nih.

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