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

• 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
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%
 14%

13% 69%
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
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
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):25

http://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 Abacavir, emtricitabine (FTC), zidovudine (AZT), didanosine
(DDI), zalcitabine (DDC), lamivudine (3TC), tenofovir
transcriptase inhibitors (NRTIs) (disoproxil fumarate), and stavudine (D4T)

Nonnucleoside reverse transcriptase Efavirenz (EFV), etravirine, nevirapine, and

inhibitors (NNRTIs) 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 Ritonavir
In clinical trials: Cobicistat

Fusion entry inhibitors Enfuvirtide

CCR5 entry inhibitors Maraviroc

In clinical trials: Vicriviroc , Monoclonal Abs: ibilazumab,
PRO140

Integrase inhibitors Raltegravir

In 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

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
• 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)

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)
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
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
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
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.
Liddicoat et al., 2004. J Gen Intern Med. 19:349
Gongidi et al., 2010. JAOA. 110:712
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 behaviors
3. HIV screening should be included in the routine panel of
prenatal screening tests for ALL pregnant women
4. 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%)
Koplan et al., 2001. MMWR. Vol. 50; RR-11
Parthasarathy et al., 2007. Ind J Anaesth. 51;91
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
Parthasarathy et al., 2007. Ind J Anesth. 51;91
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

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

 Exposure HIV Infection Status of Source

Asymptomatic Symptomatic HIV HIV unknown

HIV or known infection, AIDS, acute status
low viral load seroconversion, or
known high viral load

Less severe; Recommend Recommend No PEP usually

Solid needle and 2-drug PEP 3-drug PEP 2-drug PEP if patient
superficial injury has risk factors
More severe; Recommend Recommend No PEP usually
Hollow needle, deep 3-drug PEP 3-drug PEP 2-drug PEP if patient
puncture, blood on has risk factors
device, or needle in
patient artery or vein
Mucous membranes; Consider Recommend No PEP usually
nonintact skin; small 2-drug PEP 2-drug PEP 2-drug PEP if patient
volume (few drops) has risk factors

Mucous membranes; Recommend Recommend No PEP usually

nonintact skin; large 2-drug PEP 3-drug PEP 2-drug PEP if patient
volume (major blood has risk factors
splash)

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

 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%

S. Rerks-Ngarm, et al. 2009. NEJM. 361(2):2209 QA Karim, et al. 2010. Science. 329:1168
http://www.cdc.gov/hiv/resources/factsheets/circumcision.htm RM Grant, et al. 2010. NEJM. 363(27):2587
Thank you.
Any Questions?