Aids Updateaskdnc

AIDS/HIV UPDATENeal R. Chamberlain, Ph.D.

Associate ProfessorDepartment 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• 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

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

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

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

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

; 75% ; 25%

13% 69%

14%

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

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

EtiologyHIV-1 found worldwide- Most common in US

HIV-1 has 4 groups- M, N, O, and PM group causes most human infections9 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

RetrovirusEnveloped, diploid, single-stranded, positive-sense RNA virusesDNA intermediate, which is an integrated viral genome (a

provirus) that persists within the host-cell DNA

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

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.

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

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

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

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):25http://update.anaesthesiologists.org/wp-content/uploads/2009/10/HIV-and-Anaesthesia.pdf

HAART Therapy

CCR5 Entry Inhibitors

Class of Antiretroviral Drug Drug Names

Nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs)

Abacavir, emtricitabine (FTC), zidovudine (AZT), didanosine (DDI), zalcitabine (DDC), lamivudine (3TC), tenofovir

(disoproxil fumarate), and stavudine (D4T)

Nonnucleoside reverse transcriptase inhibitors (NNRTIs)

Efavirenz (EFV), etravirine, nevirapine, and delavirdine

In clinical trials: Rilpivirine, GSK2248761 (Viiv) and RDEA806 (Ardea)

Protease inhibitors (PIs) Amprenavir, atazanavir, darunavir, fosamprenavir, indinavir, lopinavir/ritonavir, nelfinavir (NFV),

ritonavir, saquinavir, and tipranavir

Pharmacokinetic Enhancers RitonavirIn clinical trials: Cobicistat

Fusion entry inhibitors

Enfuvirtide

CCR5 entry inhibitors MaravirocIn clinical trials: Vicriviroc , Monoclonal Abs: ibilazumab,

PRO140

Integrase inhibitors RaltegravirIn clinical trials: Elvitegravir, S/GSK1349572

Maturation Inhibitors (new class) In clinical trials: Bevirimat and Vivecon (MPC-9055)

*HAART, highly active antiretroviral therapy. Note: This list is likely to be incomplete because new antiretroviral drugs are rapidly being approved.

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)

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


HAART Therapy• Selection of HAART therapy• Treatment for naïve HIV patients

• NNRTI OR a PI OR an integrase inhibitor PLUS 2-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 (integrase inhibitor+NRTI/NRTI)


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


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


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):25http://update.anaesthesiologists.org/wp-content/uploads/2009/10/HIV-and-Anaesthesia.pdf

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

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.

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

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

Testing Patients for HIV• Testing for HIV is strongly encouraged by the CDC

1. 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)

2. Annual HIV testing for individuals with high-risk behaviors3. HIV screening should be included in the routine panel of

prenatal screening tests for ALL pregnant women4. Repeat screening in the third trimester is recommended in

certain jurisdictions with elevated rates of HIV infection among pregnant women

5. Incorporation of permission for HIV testing into general consent forms

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

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%)

Parthasarathy et al., 2007. Ind J Anaesth. 51;91

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

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

Parthasarathy et al., 2007. Ind J Anesth. 51;91Koplan et al., 2001. MMWR. Vol. 50; RR-11

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


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™)


Exposure HIV Infection Status of Source

Asymptomatic HIV or known low viral load

Symptomatic HIV infection, AIDS, acute

seroconversion, or known high viral load

HIV unknown status

Less severe;Solid needle and superficial injury

Recommend 2-drug PEP


No PEP usually2-drug PEP if patient

has risk factors

More severe; Hollow needle, deep puncture, blood on device, or needle in patient artery or vein




has risk factors

Mucous membranes; nonintact skin; small volume (few drops)

Consider 2-drug PEP



has risk factors

Mucous membranes; nonintact skin; large volume (major blood

splash)




has risk factors


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

http://www.cdc.gov/hiv/resources/factsheets/circumcision.htmS. Rerks-Ngarm, et al. 2009. NEJM. 361(2):2209

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

Thank you. Any Questions?

Date post:	14-Feb-2016
Category:	Documents
Upload:	vinaysakaleshpuramallikarjuna
View:	8 times
Download:	0 times

Aids Updateaskdnc

Documents