HIV Update. Divya Ahuja, MD Associate Professor of Medicine University of South Carolina School of Medicine

Transcription

1 HIV Update Divya Ahuja, MD Associate Professor of Medicine University of South Carolina School of Medicine Rates of Diagnoses of HIV Infection among Adults and Adolescents, 2012 United States and 6 Dependent Areas N = 48,651 Total Rate = 18.4 Note. Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. All displayed data have been statistically adjusted to account for reporting delays, but not for incomplete reporting. 1

2 Figure 11 Top 10 MSAs by AIDS Diagnosis Rate, per 100,000 Population, 2009 Miami, FL Baton Rouge, LA Jacksonville, FL New York, NY-NJ-PA Washington, DC-VA-MD-WV Columbia, SC Orlando, FL Memphis, TN-MS-AR New Orleans-Metairie-Kenner, LA Baltimore, MD U.S. Rate = 11.2 Note: MSA=Metropolitan Statistical Area. Includes MSAs with 500,000 or more population. Source: CDC, HIV Surveillance Report, Vol. 21,

3 What is the Diagnosis? 3

4 Acute Retroviral Syndrome: Signs and Symptoms - I Fever 96% Lymphadenopathy 74% Pharyngitis 70% Rash 70% Myalgia or arthralgia 54% Diarrhea 32% Always consider HIV in the differential CD4+ Cells (T helper cells) The cell type in the body that HIV infects and destroys The CD4 number tells us the state of the immune system Normal levels are Below 200, patient has AIDS 4

5 CD4 (T cell) Count Used to determine when to start ART Any CD4 is an indication to start therapy but definitely should be recommended if <500 Recheck 4 weeks after starting therapy and then every 4-6 months once stable CD4 increases as the HIV Viral Load decreases on ART Adequate response: CD4 increase cells/µl per year HIV Viral Load Measures the amount of HIV virus RNA present in the blood HIV RNA (Viral Load) Critical in determining response to ART Goal of ART: HIV RNA below limit of detection (ie, <20-75 copies/ml, depending on assay) Monitor every 3-6 months to look for response to therapy Undetectable does not mean uninfected 5

6 Plasma HIV RNA CD4 Count, Viral Load, and Clinical Course Primary Infection Seroconversion 10,000,000 1,000, ,000 10,000 1, Intermediate Stage AIDS Viral Load CD4 Cells high risk of opportunistic infections 4-8 Weeks Up to 12 Years 2-3 Years CD4 Cell Count 1, Opportunistic Infections (O.I.s ) Occur due to immunsuppression Prophylaxis for patients with low CD4 counts Examples PCP, Toxoplasmosis, MAC, etc 6

7 Prophylaxis for Selected OIs Primary Prophylaxis Pneumocystis jiroveci pneumonia (PCP)- if CD4 < 200; TMP/SMX Mycobacterium avium complex (MAC)- if CD4< 50; azithromycin Toxoplasmosis- if CD4 < 100; TMP/SMX Tuberculosis -PPD S pneumoniae infections- Vaccinate Hepatitis A and B - Vaccinate Influenza- Vacccinate Oral Candidiasis 7

8 Case 39 yr male, presents to ER with seizures New Diagnosis of HIV Cerebral toxoplasmosis in an AIDS patient. Infection acquired from cat litter, uncooked meats Pneumonia in HIV Streptococcus. pneumoniae is increased > 100 fold PCP Tuberculosis Other atypical pathogens Cryptococcus Histoplasma 8

9 PCP: Imaging 6/05 Chest x ray: PCP pneumonia with bilateral, diffuse granular opacities. Credit: L, Huang, MD, HIV InSite Chest x ray: PCP pneumonia with bilateral perihilar opacities, interstitial prominence, hyperlucent cystic lesions. Credit: HIV Web Study, org, 2006 University of Washington HIV and STDs 28 year HIV positive male with CD4 of 250 Fever, malaise and a rash Sex with a number of male partners Diagnosis: Syphilis 9

10 Genital Warts Atlas fig 8.13 Page 297 Condylomata acuminata Smooth papular warts Keratotic flat wart Flat cervical condylomata 10

11 Goals of Treatment for HIV Reduce HIV-related morbidity; prolong duration and quality of survival Restore and/or preserve immunologic function Maximally and durably suppress HIV viral load Prevent HIV transmission May Association of CD4+ Cell Count Nadir With Clinical Outcomes Low CD4+ count nadir associated with Increased rates of HIV-associated neurocognitive disorders Arterial stiffness contributing to CV risk Coronary heart disease Malignancies including Lymphoma, lung cancer Increased risk of fracture 1. Ellis R, et al. AIDS. 2011;25: Ho J, et al. AIDS ;24: Klein D, et al. CROI Abstract Young B, et al. Clin Infect Dis. 2011;52:

12 Potential Benefits of Early Therapy Potential decrease in risk of many complications, including: HIV-associated nephropathy Liver disease progression from hepatitis B or C Cardiovascular disease Malignancies (AIDS defining and non-aids defining) Neurocognitive decline Blunted immunological response owing to ART initiation at older age Persistent T-cell activation and inflammation May Recommendations for Initiating ART When to start ART is recommended for all HIVinfected individuals to reduce the risk of disease progression. The strength of this recommendation varies on the basis of pretreatment CD4 count (stronger at lower CD4 levels) ART also is recommended for HIVinfected individuals for the prevention of transmission of HIV. May

13 Recommendations for Initiating ART: CD4 Count or Clinical Category Recommended for all CD4 counts: CD4 count <350 cells/µl (AI) CD4 count cells/µl (AII) CD4 count >500 cells/µl (BIII) May Anti-Retroviral Therapy (ART) Collective name given to the HIV medications that patients are on Medications must be taken daily Take all or not at all, each day Missing medications can cause problems 13

14 NRTI Abacavir (ABC) Didanosine (ddi) Emtricitabine (FTC) Lamivudine (3TC) Stavudine (d4t) Tenofovir (TDF) Zidovudine (AZT, ZDV) NNRTI Delavirdine (DLV) Efavirenz (EFV) Etravirine (ETR) Nevirapine (NVP) Rilpivirine (RPV) March 2012 Current ARV Medications PI Atazanavir (ATV) Darunavir (DRV) Fosamprenavir (FPV) Indinavir (IDV) Lopinavir (LPV) Nelfinavir (NFV) Ritonavir (RTV) Saquinavir (SQV) Tipranavir (TPV) Integrase Inhibitor (II) Raltegravir (RAL) Elvitegravir Dolutegravir Fusion Inhibitor Enfuvirtide (ENF, T-20) CCR5 Antagonist Maraviroc (MVC) What to start?: DHHS Guidelines 2014 Recommended Regimens PI Based Boosted atazanavir + tenofovir+emtricitabine (Truvada) Boosted darunavir (daily) +Truvada NNRTI based Efavirenz+tenofovir+emtricitabine (Atripla) Integrase Inhibitor Based Raltegravir + Truvada Stribild Dolutegravir + Truvada Dolutegravir + Epzicom 14

15 What to start?: DHHS Guidelines 2014 Recommended Regimens With the caveat that the baseline viral load is < 100,000 copies/ml Efavirenz + Epzicom Boosted reyataz + Epzicom With the caveat that the baseline viral load is < 100,000 copies/ml and CD4 count >200 cell/mm 3 Complera (Riplivirine + Epzicom as FDC) CBC CMP G6PD Lipids RPR Pre ART work up Hep A antibody, Hep B s Ag and Ab, Hep C Ab PPD UA and calculated creatinine clearance Urine for GC/Chlamydia (and extragenital May sites) 15

16 Additional testing Toxoplasma IgG Serum Cryptococcal antigen if CD4 < 100 Ophthalmology evaluation if CD4 < 50 Trichomonas testing Pap test at initiation of care and annually Morning Serum testosterone (optional) Blood Cultures for AFB if CD4 < 50 May Anti-Retroviral Therapy (ART) Classes of ART Non-nucleoside reverse transcriptase (NNRTI) Nucleoside reverse transcriptase (NRTI) Protease inhibitors (PI) Integrase inhibitors Fusion inhibitors ART regimen consists of a combination of two or more classes of medication 16

17 HIV Treatment: Single Tablet Regimens Atripla Complera Stribild Triumeq 17

18 Chemokine Receptor Blockers First (and only) chemokine receptor blocker FDA approved in fall, 2007: Maraviroc (Selzentry) Co-receptor tropism assay (Trofile assay) should be performed before using a CCR5 inhibitor Mechanism of action- Maraviroc: Allosteric inhibitors CCR5 chemokine receptor 18

19 Fusion Inhibitor Enfuvirtide- Fuzeon, T20 Prevents HIV attachment, fusion and entry into the host cell It is a subcutaneous injection Rarely used anymore Nucleoside Reverse Transcriptase Inhibitors Mechanism of action Competitively blocks the reverse transcriptase enzyme active site Causes chain termination 19

20 Nucleotide RTI Tenofovir (TDF, Viread) Also active against chronic HBV Adefovir (FDA approved for Hepatitis B). The dose needed to treat HIV is too toxic. Lamivudine (3TC, Epivir) Emtricitabine (FTC, Emtriva) Both active against Hepatitis B Emtriva is co-formulated with tenofovir (Truvada) Question Which antiretroviral drugs require dose adjustment for CKD? Zidovudine Lamivudine Emtricitabine Tenofovir Didanosine Stavudine All the currently available nucleosides except abacavir 20

21 Nonnucleoside RTI Mechanism of action Noncompetitively blocks reverse transcriptase enzyme active sites Efavirenz-Sustiva Nevirapine-Viramune Second Generation non-nuke Etravirine- Intelence Rilpivirine - Endurant 21

22 Integrase Inhibitors Mechanism of action- Interferes with viral enzyme that allows for covalent linkage of viral DNA to the cellular DNA Current Integrase Inhibitors Raltegravir (Isentress) Elvitegravir- FDA approved as part of Stribild (formerly know as the QUAD pill) Dolutegravir (Tivicay)- FDA approved 8/12/13 Boosted Protease Inhibitors Ritonavir is used almost exclusively to boost other PI levels 22

23 Protease Inhibitors Darunavir (Prezista) Dose 600 mg (1 pill) BID boosted with 100 mg (1 pill) BID of ritonavir Dose: 800 mg (1 pill) darunavir with 100 mg (1 pill) ritonavir Atazanavir- Can cause hyperbilirubemia, Gilbert s like syndrome Drug interactions with PPI (amongst others) As estimated by the CDC: The percentage of HIV infected individuals older than 50 years, in the year 2015 will be: 1. a. 20% 2. b. 25% 3. c. 30% 4. d. 50% 5. 23

24 HIV and the Older Patient: ART ART is recommended in patients >50 years of age, regardless of CD4 cell count (BIII) Older persons have decreased immune recovery and increased risk of non-aids events Non-AIDS illnesses (eg, cardiovascular disease, liver disease, cancer, bone fragility, and neurocognitive impairment) may have increased disease burden in aging HIV-infected persons November Comorbidities not only more common with increasing age but also occur earlier in HIV Co-mobidities prevalence in cases and controls, stratified by age categories. The following co-morbidities were analysed: Hypertension, Type 2 Diabetes, Cardiovascular Disease and Osteoporosis. Co-morbidities prevalence was higher in cases than controls in all age strata (all p-values <0.001). Guaraldi G et al. Clin Infect Dis 2011; 53:

25 Common Drug Interactions with ARVs: Require Dosage Modification or Cautious Use Oral hormonal contraceptives, including emergency contraception (Plan B): may require alternative or second method Methadone Erectile dysfunction agents Herbs St. John s wort Acid-lowering medications (some may be contraindicated, eg, with ATV or RPV) Hepatitis C NS3/4A protease inhibitors (many contraindicated ARVs) May Testing for Drug Resistance Before initiation of ART: Transmitted resistance in 6-16% of HIV-infected patients In absence of therapy, resistance mutations may decline over time and become undetectable by current assays Recommended for all pregnant women Patients with virologic failure: Perform while patient is taking ART, or 4 weeks after discontinuing therapy May

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27 Perinatal Transmission of HIV Without antiretroviral prophylaxis - 16% 25% Today, with highly active antiretroviral therapy (HAART), elective C/S as appropriate and formula feeding <1% Cases according to timing of transmission In utero Intrapartum 25% 40% of cases 60% 75% of cases Perinatal Transmission of HIV Any CD4 value After 1 st trimester but can continue medications if already on them. (some medications are harmful to the fetus) Use ART per DHHS guidelines Goal: To get the viral load < 20 ASAP 27

28 Immune Reconstitution Inflammatory Syndrome Characterized by fever, worsening clinical signs of the OI; symptoms of new OI Associated with a rise in CD4 and/or a fall in viral load Usually occurs within first few weeks of ART but may occur up to several months later Immune Reconstitution Syndrome Mycobacterial infections Pneumocystis jiroveci pneumonia (PCP) Toxoplasmosis Hepatitis B, hepatitis C Workup and management Evaluate for new OI or drug toxicity Consider NSAIDs or corticosteroids Cytomegalovirus infection Varicella-zoster infection Cryptococcal infection Progressive multifocal leukoencephalopathy (PML) KS 28

29 HCV/HIV Coinfection Higher rates of progressive liver disease ART may slow progression of liver disease ART is recommended for most coinfected patients, regardless of CD4 count If CD4 count low (eg, <200 cells/µl), start ART quickly; may delay HCV therapy until stable on ART For most patients, benefits of ART outweigh concerns about ARV-associated hepatotoxicity November Burden of Hepatitis C Virus Morbidity and Mortality Among Persons Born % of the US population (3.2 million) is infected with Hepatitis C Chronic HCV is the commonest cause of liver transplant in the US Prevalence of hepatitis C virus (HCV) in baby boomers is about 4% Represents 81% of all US adult chronic HCV infections 1. Smith, et al. American Association for the Study of Liver Disease Liver Meeting, San Francisco, CA Armstrong, et al. Ann Int Med Kramer, et al. Hepatology

30 Recent recommendations USPSTF (June 2013) and CDC ( August 2012): Screen adults at risk for HCV infection PLUS Screen adults born 1945 through 1965 One-time testing for HCV without prior ascertainment of HCV risk factor Smith BD et al. MMWR Morb Mortal Wkly Rep. 2012;61:

31 Suggested current strategy Test for Hepatitis C (Antibody and PCR) And HIV Vaccinate ; Hep A and Hep B Stage liver damage; non-invasive test or liver biopsy and Metavir score Treat everybody with Metavir F3 or greater and individualize treatment for those with F0, F1, F2 disease Participate in a Tele-health program 31