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AIDS/HIV Update. Neal R. Chamberlain, Ph.D. Associate Professor Department of Microbiology/Immunology A.T. Still University/Kirksville College of Osteopathic Medicine. Introduction- US HIV Epidemic. The HIV epidemic has claimed more than 575,000 lives

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AIDS/HIV Update

Neal R. Chamberlain, Ph.D.

Associate Professor

Department of Microbiology/Immunology

A.T. Still University/Kirksville College of Osteopathic Medicine


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Introduction- US HIV Epidemic

  • The HIV epidemic has claimed more than 575,000 lives

  • The CDC estimates that there are from 500,000 to 1.1 million individuals living with HIV

  • Nearly 18,000 AIDS patients die each year

  • Around 56,000 new HIV infections are reported annually

  • Every 9 minutes and 30 seconds someone is infected with HIV

http://www.cdc.gov/hiv/resources/factsheets/us.htm

HIV prevalence estimates—US, 2006. MMWR 2008;57(39):1073

Hall et al. Estimation of HIV Incidence in the US. JAMA2008;300: 520


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Introduction- US HIV Epidemic

  • 21% of the persons living with HIV do not know their HIV status (105,000-231,000 persons)

    • Due to the fact that they have not been tested

    • Higher percentages of those unaware of their HIV status were observed in high prevalence groups (MSM)

  • Transmission rate in undiagnosed persons is 3.5 times higher than in those that know their HIV status

  • The overall transmission rate is 5 per 100 person years


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Introduction- US HIV Epidemic

  • Transmission rate in those treated with HAART is 0.46 per 100 person years

  • Studies of heterosexual discordant couples observed no transmission in patients treated with HAART (viral load below 400/ml)

  • Identifying those infected and living with HIV is essential and should significantly reduce the spread of this virus in the US


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; 75%

; 25%


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14%

13%

69%


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Hall HI et al. Estimation of HIV Incidence in the US. JAMA 2008; 300:520


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Epidemiology- Summary

  • Numbers of those living with HIV are increasing

  • Most common in those 20-45 years of age

  • 0ne in five don’t know they are infected with HIV

    • 31% diagnosed with HIV late in the infectious process

    • Transmission rates higher in those that don’t know they are infected

  • 75% of new infections are seen in males

    • Most common means of transmission in males: MSM

    • Numbers of new infections increasing in MSM

    • Most common means of transmission in females: heterosexual interactions

  • High levels of HIV infection in African American and Hispanic/Latino populations

Hall et al. Estimation of HIV Incidence in the US. JAMA 2008; 300:520


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Etiology

  • HIV-1 found worldwide- Most common in US

    • HIV-1 has 4 groups- M, N, O, and P

    • M group causes most human infections

    • 9 subtypes and various CRF subtypes

    • B subtype most common in US, Europe, and South America.

    • C subtype most common in sub-Saharan Africa

  • HIV-2 endemic in west Africa- rare cause of US infections

  • Retrovirus

    • Enveloped, diploid, single-stranded, positive-sense RNA viruses

    • DNA intermediate, which is an integrated viral genome (a provirus) that persists within the host-cell DNA


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Transmission

  • Routes of infection

    • Sexual

      • Anal

      • Vaginal

      • Homosexual- most common in adult males

      • Heterosexual- most common in adult females

    • Percutaneous

      • Transfusions

      • Needle sharing

      • Needle stick

    • Maternal-child

      • Transplacental

      • Peripartum

      • Breast milk ingestion


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Manifestations

  • 3 different stages

    • Primary HIV infection

    • Asymptomatic HIV infection

    • AIDS

  • Many patients are asymptomatic until stage 3

  • Those infected with HIV are infectious to others in all stages

  • Stage 1 ends when high titers of anti-HIV antibodies are produced

  • Detectable levels of anti-HIV antibodies are usually observed in 2-4 weeks.


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Course of Infection

  • Time varies by host factors and viral factors

    • Rapid progressors- AIDS in 2-3 yrs

    • Typical progressors- AIDS in 10 yrs

    • Long-term nonprogressors- low HIV levels; normal CD4+ T cells; >10 yrs after HIV positive

      • Bone marrow transplant case

    • Highly-exposed persistently seronegative patients- infected but no HIV antibodies or HIV-RNA detected

    • Disease progresses faster in certain subtypes of HIV


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Pathogenesis

  • HIV destruction of CD4-T cells and macrophages causes immunosuppression

  • Killing of CD4-T cells destroys ability to mount immune response to infectious agents and to eliminate tumor cells.

  • More severe the disease the lower the CD4-T cell numbers and greater the amount of virus in blood stream.

CJ Miller, HIV transmission: Migratory Langerhans cells are primary targets in vaginal HIV transmission Immuno Cell Biol (2007) 85:269


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Diagnosis

  • Usually there are no unique signs or symptoms

  • High index of suspicion- Hx high risk behaviors, unusual infections and symptoms

  • Laboratory testing

    • Screening tests

      • ELISA or EIA

      • EIA- rapid testing (e.g., OraQuick)- can use whole blood, plasma, or oral secretions

    • Confirmatory tests

      • Western Blot analysis

      • RT-PCR


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HIV, Surgery, and Anesthetics

  • Blood transfusion can cause increases in HIV viral load. Blood should be transfused only if unavoidable

  • Pain is common in patients with advanced HIV disease

    • It is multifactorial and can be difficult to treat

      • Opportunistic infections, HIV-related arthralgia, peripheral neuropathy, and drug-related pain

      • HIV infection may affect the treatment of postoperative pain

  • HIV infection is NOT an absolute contraindication to regional anesthesia

    • Certain complications associated with HIV may pose relative contraindication to regional anesthesia

      • Myelopathy, vertebral or spinal neoplasms, CNS infections, and coagulopathy

S Wilson, HIV and Anaesthesia, 2009. Update in Anaesthesia, 25(2):25

http://update.anaesthesiologists.org/wp-content/uploads/2009/10/HIV-and-Anaesthesia.pdf


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HAART Therapy

CCR5 Entry

Inhibitors


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HAART Therapy

  • Selection of HAART

    • HAART (Highly Active Antiretroviral Therapy)-

      • Fewer opportunistic infections

      • Prolongs the life of HIV-infected patients.

    • Successful HAART (available since 1996)

      • Suppresses HIV replication.

      • Halts damage and partially restores the immune system and its function.

Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for use of antiretroviral

Agents in HIV-1-infected adults and adolescents. Department of Health and Human Services.

January 10, 2011; 1-166.

http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf (Accessed 1/15/2011)


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HAART Therapy

  • When to start HAART

    • All Pt with hx of AIDS-defining condition or CD4 T-cell count of <350 cells/mm3

    • All Pt that are pregnant, HIV nephropathy, HBV co-infection when HBV Rx is needed

    • Recommended for all Pt with 350-500 cells/mm3

    • Optional for Pt with >500 cells/mm3

Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for use of antiretroviral

Agents in HIV-1-infected adults and adolescents. Department of Health and Human Services.

January 10, 2011; 1-166.

http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf (Accessed 1/15/2011)


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HAART Therapy

  • Selection of HAART therapy

  • Treatment for naïve HIV patients

    • NNRTI OR a PI OR an integrase inhibitor PLUS2-NRTIs

  • Four regimens are now listed as “Preferred” regimens:

    • Efavirenz + tenofovir/emtricitabine(NNRTI+NRTI/NRTI)

    • Ritonavir-boosted atazanavir + tenofovir/emtricitabine (PI-PI+NRTI/NRTI)

    • Ritonavir-boosted darunavir + tenofovir/emtricitabine (PI-PI+NRTI/NRTI)

    • Raltegravir+ tenofovir/emtricitabine (integraseinhibitor+NRTI/NRTI)

  • Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for use of antiretroviral

    Agents in HIV-1-infected adults and adolescents. Department of Health and Human Services.

    January 10, 2011; 1-166.

    http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf (Accessed 1/15/2011)


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    Therapy- Adverse effects of HAART

    • Four major groups

      • Mitochondrial dysfunction: lactic acidosis, hepatic toxicity, pancreatitis, peripheral neuropathy

      • Metabolic abnormalities: fat maldistribution and change in body habitus, dyslipidemia, hyperglycemia and insulin resistance, bone disorders (e.g. osteopenia, osteoporosis and osteonecrosis)

      • Bone marrow suppression: anemia, neutropenia and thrombocytopenia

      • Allergic reactions: skin rashes and hypersensitivity responses

    S Wilson, HIV and Anaesthesia, 2009. Update in Anaesthesia, 25(2):25

    http://update.anaesthesiologists.org/wp-content/uploads/2009/10/HIV-and-Anaesthesia.pdf


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    Therapy- HAART and Anesthetics

    • Due to viral drug resistance it is recommended that HAART be continued throughout the perioperative period if at all possible

    • Anesthetic agents can induce pharmacodynamic changes that influence the efficacy and toxicity of HAART agents

    • HAART can affect the absorption, distribution, metabolism and elimination of anesthetic agents

      • PI’s and NNRTI’s are the most commonly implicated HAART agents associated with drug interactions

      • Halothane or methoxyflurane with HAART can cause hepatic or renal dysfunction

      • Propofol and NRTIs taken together may promote mitochondrial dysfunction and lactic acidosis

    S Wilson, HIV and Anaesthesia, 2009. Update in Anaesthesia, 25(2):25

    http://update.anaesthesiologists.org/wp-content/uploads/2009/10/HIV-and-Anaesthesia.pdf


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    Therapy- HAART and Anesthetics

    • Opioids-

      • Fentanyl may be enhanced by ritonavir due to both liver enzyme inhibition and induction. Enzyme inhibition reduces fentanyl clearance and enzyme induction increases metabolism to active metabolites such as normepiridine.

      • Methadone clearance can be affected by some HAART agents and methadone can affect the clearance of some HAART agents

    • Benzodiazepines-Saquinavir may inhibit midazolam metabolism.

    • Local anesthetics- such as lidocaine may have increased plasma levels due to enzyme inhibition.

    • Neuromuscular blocker- effects may be prolonged, even a single dose of vecuronium

    • Calcium channel blockers- may have enhanced hypotensive effects due to enzyme inhibition.

    S. Wilson, HIV and Anaesthesia, 2009. Update in Anaesthesia, 25(2):25

    http://update.anaesthesiologists.org/wp-content/uploads/2009/10/HIV-and-Anaesthesia.pdf


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    Prevention- Protecting Yourself

    • Screening of patients, blood supply, and of tissues to be transplanted

    • Do your patients know their HIV status?

      • Test those at low risk for HIV infection at least once in their life

      • Those living in areas of high HIV prevalence should be screened more frequently

      • Test those at high risk for HIV infection annually. Some suggest twice a year testing in high risk groups

    • Screen pregnant women for HIV and treat HIV positive women to prevent passage of the virus to the child

      • Current recommendations: treat with HAART no matter what their CD4-T cell count

    Vital Signs: HIV Testing and Diagnosis Among Adults- United States, 2001-2009.

    December 3, 2010. MMWR. 59(47): 1550


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    Testing Patients for HIV

    • Many HIV positive individuals are diagnosed late in the course of their disease (32.3%)

    • Transmission rates are higher in undiagnosed HIV infected persons than in those who know their HIV status

    • In one study it took 5 visits on average by the patient to the same healthcare facility before a dx of HIV infection was made

    • Recent study in JAOA- 22% of primary care DO’s recommended HIV testing to their patients during their initial visit

    • Osteopathic physicians who were women, African American, or Hispanic were more likely to screen patients for HIV than other DO’s.

    Liddicoat et al., 2004. J Gen Intern Med. 19:349

    Gongidi et al., 2010. JAOA. 110:712


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    Testing Patients for HIV

    • Testing for HIV is strongly encouraged by the CDC

      • HIV screening is recommended for patients (13-64 years of age) in ALL health-care settings after the patient is notified that testing will be performed unless the patient declines (opt-out screening)

      • Annual HIV testing for individuals with high-risk behaviors

      • HIV screening should be included in the routine panel of prenatal screening tests for ALL pregnant women

      • Repeat screening in the third trimester is recommended in certain jurisdictions with elevated rates of HIV infection among pregnant women

      • Incorporation of permission for HIV testing into general consent forms

    Branson et al., 2006. MMWR. 55(RR14);1-17


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    Prevention- Protecting Yourself

    • Adopt universal infection control precautions for ALL patients

      • Especially if you practice in areas of high HIV prevalence

      • 20% of anesthesiologists had at least one needle stick injury in the past 3 months

      • High prevalence area; risk acquiring HIV- 4.5% during a 30yr career

    • Post-Exposure Prophylaxis- Know what to do in advance!

    • Anesthesiologists can acquire HIV during their work via:

      • sharp injuries (risk of HIV transmission 0.3%),

      • contamination of broken skin with the patients’ body fluids (risk of HIV transmission <0.1%), and

      • splashing HIV containing body fluid in the eyes, nose or mouth (risk of HIV transmission 0.1%)

    Koplan et al., 2001. MMWR. Vol. 50; RR-11

    Parthasarathyet al., 2007. Ind J Anaesth. 51;91


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    Post-Exposure Prophylaxis

    • Several body fluids can transmit HIV.

    • They include:

      • Blood and fluid containing visible blood

      • Semen, vaginal secretions, and cerebrospinal, synovial, pleural, peritoneal, pericardial, and amniotic fluids

    • Human tissues can also transmit HIV

    • Factors which increase transmission of HIV

      • Hollow needle injuries

      • Injury by a device visibly contaminated with the patient’s blood

      • The injury resulted from a device placed in the patient’s vein or artery

      • Deep injuries

      • Exposure to blood from source persons with primary or terminal HIV illness

    Koplan et al., 2001. MMWR. Vol. 50; RR-11

    Parthasarathyet al., 2007. Ind J Anesth. 51;91


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    Post-Exposure Prophylaxis

    • Clean wound with soap and water; mucosal exposures rinse with water

    • Report the exposure to the appropriate department (e.g., infection control, occupational health)

    • Start the HIV PEP regimen as soon as possible (within 2 hrs)

    • Treat for 4 weeks

    • If source is tested and found to be HIV negative discontinue PEP

    Branson et al., 2006. MMWR. 55(RR14);1-17


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    Post-Exposure Prophylaxis

    • Recommendations for HIV PEP include a basic 4-week regimen of 2 drugs

      • Zidovudine (Retrovir™) and lamivudine (Epivir™) (Combivir™ - contains both zidovudine and lamivudine),

      • Lamivudine (Epivir™) and stavudine (Zerit™), OR

      • Didanosine (Videx™) and stavudine (Zerit™)

    • An expanded regimen that includes the addition of a 3rd drug for HIV exposures that pose an increased risk for transmission

      • Indinavir (Crixivan™), Nelfinavir (Viracept™), Efavirenz (Sustiva™), or Abacavir (Ziagen™)

    Branson et al., 2006. MMWR. 55(RR14);1-17


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    Branson et al., 2006. MMWR. 55(RR14);1-17


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    Vaccines/Recent Prevention Studies

    • Thai vaccine study demonstrated limited success.

      • Immunization reduced HIV infections by around 31%

    • Male circumcision is associated with lower risk for HIV

      • May reduce male-to-female transmission; lesser extent on female-to-male transmission

    • Tenofovir gel for prevention of HIV infection in women

      • HIV incidence lowered as much as 54% in high adherence subjects; intermediate adherers (38%); low adherers (28%)

      • Followed for 30 months; insert gel within 12hr before sex and a second dose as soon as possible within 12hr after sex

    • HIV oral pre-exposure prophylaxis trial (iPrEx study)

      • Once daily Truvada (tenofovir and emtricitabine); Lowered risk of getting HIV in gay men and transgender women by 44%

    QA Karim, et al. 2010. Science. 329:1168

    S. Rerks-Ngarm, et al. 2009. NEJM. 361(2):2209

    RM Grant, et al. 2010. NEJM. 363(27):2587

    http://www.cdc.gov/hiv/resources/factsheets/circumcision.htm


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    Thank you. Any Questions?


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