1. Lam Do, Pharm D. Candidate Clinical Seminar II October 24, 2013
HIV/AIDs
Lam Do, Pharm D. Candidate
Clinical Seminar II
October 24, 2013

2. definitions
HIV-1 – More virulent and infective form of the virus and is the cause of the majority of HIV infections
HIV-2 – has a distinct form but related to HIV-1. Primarily found in West Africa.
Less pathogenic and do not have progressive disease but can lead to immunosuppression and AIDS
AIDS – acquired immune deficiency syndrome, is an infections disease cause by the human immunodeficiency virus

3. PREVALENCE and incidence
CDC estimates 50,000 people are newly infected with HIV each year
In 2010, there were an estimated 47,500 new HIV infections
In 2010, an estimated 15,529 people with AIDS died
Approximately 636,000 people in the United States died since the epidemic begin
In 2011, an estimated 49,273 people were diagnosed with HIV infection in the United States
32,052 people were diagnosed with AIDS
1,155,792 people have been diagnosed with AIDS since the epidemic begin

5. epidemiology
By the end of 2009, an estimated 33.3 million individuals were living with HIV infection
More than 95% of people living with HIV/AIDS reside in low and middle income countries
50% are female
2.5 million are child <15 years

6. Risk factors/transmissions
Men who have sex with men without a condom
Sharing needles by injecting drugs or steroids
Have a sexually transmitted infection syphilis, genital herpes., gnorrhea, bacterial vaginosis, trichonomoniasis
Diagnosed with hepatitis, tuberculosis, or malaria
Exposed to the virus as a fetus or infant before birth or breastfeeding from an infected mother
Received a blood transfusion between 1978 to 1985

7. pathophysiology

8. symptoms Early stages: Fever Headache Tiredness
Enlarged lymph nodes in the neck and groin area
Later symptoms:
Rapid weight loss
Recurring fever or night sweats
Extreme tiredness
Prolonged swelling of the lymph glands in the armpits, groin, or neck
Diarrhea lasts more than a week
Sores of the mouth, anus, or genitals
Pneumonia
Red, brown, pink, or purplish blotches on the skin or inside the mouth, nose, and eyelids
Memory loss, depression, and other neurologic disorders

9. transmission Primary body fluids: Blood
YES NO
Primary body fluids:
Blood
Semen (ejaculate or pre-ejaculate)
Vaginal fluids
Breast milk
Tears
Sweat
Saliva
Nasal fluid
Urine
Feces
Vomit

10. Diagnosis
Viral load:
Used as a prognostic factor to monitor disease progression and effects of treatment
CD4 lymphocytes:
A surrogate marker of disease progression
Normal level cells/mm3

11. Opportunistic infections
Organisms
CD4 count (cells/uL)
Prophylaxis
Pneumoncystic Pneumonia (PCP)
<200 cells/mm3
Bactrim
Toxoplasma gondii Encephalitis
<100 cells/uL
Cryptosporidiosis
ART
Mycobacterium tuberculosis
Screening for latent tuberculosis bacterial infection (LTBI)
Isoniazid + pyridoxine x 9 months
Disseminated mycobacterium avium
<50 cells/uL
Azithromycin
Clarithromycin

12. Opportunistic infections cont.
Organisms
CD4 count (cells/uL)
Prophylaxis
Syphilis
------
Benzathine penicillin
Histoplasmosis
<150
Itraconazole
Coccidioidomycosis
<250
Fluconazole
Varicella Zoster Virus
>200, not vaccinated
Varivax vaccination
Hepatitis A Virus
Chronic liver disease
Injection drug users
Hepatitis A vaccine
Hepatitis B Virus
Not vaccinated
Engerix B

13. HIV Testing HIV Antibody test:
HIV antibodies are protein the body produces in response to HIV infection
It usually takes about 3-6 months from the time of infection to produce enough antibodies to be detected
This time period is call “window period”

14. Testing during window period
Plasma HIV RNA test (Viral load):
Detect HIV in blood within 9 days of infection, before the body develops HIV antibodies
ELISA (Enzyme-linked Immunosorbent Assay):
Detect immune responses in the body
It involves an enzyme and an antibody or antigen
Polymerase chain reaction (PCR):
Detects either RNA or DNA of HIV in while blood cells infected with the virus.

15. Testing during window period
Immunofluorescence Antibody Assay (IFA):
Detects HIV antibodies using special fluorescent dye and a microscope
Use to confirm the results of an ELISA test
Western Blot test:
Look for antibodies against HIV proteins
Proteins from HIV envelope
Proteins from the core of the virus
Enzymes that HIV uses in the process of infection

16. Rapid hiv testing
Design to be simple and quick with little to no specialized equipment
Quick results
FDA-Approved Rapid HIV Test
OraQuick Advance – oral swab or blood
Uni-Gold Recombigen – requires whole blood
Clearview Stat-Pak and Complete – requires whole blood
Reveal G-3 – requires serum or plasma
Multispot – requires serum or plasma

17. Baseline evaluation
Laboratory tests should performed during initial visits to determine HIV disease and to assist in the selection of ARV drug regimens
HIV antibody testing
CD4 T-cell count
Plasma HIV RNA
Complete blood count, chemistry profile, transaminase levels, blood urea nitrogen (BUN), creatinine, urinalysis, serologies for hepatitis A, B, and C viruses
Fasting blood glucose
Serum lipids
Genotypic resistance testing

18. Treatment Classes of Antiretroviral
Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Protease Inhibitors (PIs)
Fusion Inhibitors
Integrase Inhibitors
CCR5-receptor Antagonists

19. treatment Goal of therapy Decrease morbidity and mortality
Improve quality of life
Restore and preserve immune function
Prevent transmission and suppression of HIV replication
Highly active antiretroviral therapy (HAART)
An initial ARV regimen generally consists of two NRTIs in combination with an NNRTI, a PI (preferably boosted with ritonavir), an INSTI, or a CCR5

20. Nucleoside reverse Transcriptase inhibitors
Generic Name
Brand Name
Adult Dosing
Approval Date
Zidovudine (AZT, ZDV)
Retrovir
300mg BID; 200mg TID
1987
Didanosine (ddl)
Videx
>60kg: 600mg daily
<60kg: 250mg daily
1991; Videx EC 2000
Stavudine (d4T)
Zerit
>60kg: 40mg BID
<60kg: 30mg BID
1994
Lamivudine (3TC)
Epivir
150mg BID; 300mg Daily
1995
Abacavir (ABC)
Ziagen
300mg BID; 600mg daily
1998
Tenofovir Disoproxil Fumarate (TDF/TFV)
Vired
300mg Daily
2002
Emtricitabine (FTC)
Emtriva
200mg cap. Daily
240mg soln. Daily
2003

21. Nucleoside reverse Transcriptase inhibitors
Mechanism of Action:
Acts by competitive inhibitor of HIV reverse transcriptase
Class adverse effects:
Lactic acidosis
Hepatic steatosis
Lipodystrophy
Hyperlipidemia
Abacavir
A HLA-B-5701 screening is recommended for hypersensitivity reaction

22. Non-nucleoside reverse transcriptase inhibitors
Generic Name
Brand Name
Adult Dosing
Approval Date
Nevirapine (NVP)
Viramune
200mg daily x 14 days, then 200mg BID
1996
Delavirdine (DLV)
Rescriptor
400mg TID
1997
Efavirenz (EFV)
Sustiva
600mg at bedtime
1998
Etravirine (ETR,TMC 125)
Intelence
200mg daily
2008
Rilpivirine (RPV)
Endurant
25mg daily
2011

23. Non-nucleoside reverse transcriptase inhibitors
Mechanism of Action:
Bind directly to HIV reverse transcriptase, preventing viral conversion from RNA to DNA
Class-wide adverse effects
Rash (stevens-johnson syndrome)
Headache
Drug interactions
Mostly inducers of CYP 3A4 (some have inhibition actions)

24. Protease inhibitors Generic Name Brand name Adult Dosing Approval Date
Saquinavir (SQV)
Invirase (hard gel)
Fortovase (soft gel)
SQV 1000mg + RTV 100mg BID
1995, 1997, withdrawn 2005
Indinavir (IDV)
Crixivan
800mg q8h; IDV 800mg + RTV 100mg or 200mg BID
1996
Ritonavir (RTV)
Norvir
mg per day daily; bid as PI booster only
Nelfinavir (NFV)
Viracept
1250mg BID; 750mg TID
1997
Amprenavir (APV)
Agenerase
1400mg BID
1997, withdrawn 2007

25. Protease Inhibitors cont.
Generic Name
Brand name
Adult Dosing
Approval Date
Lopinavir/ritonavir (LPV/RTV)
Kaletra
LPV 400mg/100mg BID; or 800mg/200mg daily
2000, kaletra formulation 2005
Atazanavir (ATV)
Reyataz
400mg daily; ATV 300mg + RTV 100mg daily
2003
Fosamprenavir (fAMP, FPV)
Lexiva
1400mg bid; FPV 1400mg+RTV 200mg or FPV 700mg + RTV 100mg BID
Tipranavir (TPV)
Aptivus
TPV 500mg + RTV 200mg BID
2005
Darunavir (DRV)
Prezista
DRV 600mg + RTV 100mg BID
2006

26. Protease inhibitors cont.
Mechanism of Action
Prevent the processing of viral proteins into function formations, resulting in the production of immature, noninfectious viral particles
Adverse effects GI
Increase bleeding in hemophiliacs
Hyperlipidemia
Diabetes mellitus
Hepatotoxicity
Fat maldistribution
Drug interactions
Inhibitors of CYP 3A4

27. Combinations Generic Name Brand name Adult Dosing Approval Date
Zidovudine/Lamivudine
Combivir
1 tablet bid
1997
Zidovudine/ Lamivudine/ Abacavir
Trizivir
2000
Lamivudine/ Abacavir
Epzicom
1 tablet daily
2004
Tenofovir/ Emtricitabine
Truvada
Tenofovir/ Emtricitabine/ Efavirenz
Atripla
1 capsule daily
2006
Emtricitabine/ Rilpivirine/ Tenofovir
Complera
2011
Elvitegravir/ Covicistat/ Emtricitabine/ Tenofovir
Stribild
2012

28. Integrase inhibitors Mechanism of Action:
Generic Name
Brand Name
Adult Dosing
Approval Date
Raltegravir
Isentress
400mg BID
2007
Mechanism of Action:
Inhibition of viral DNA integration into CD4 DNA
Adverse effects
GI effects

29. Fusion inhibitor Mechanism of Action:
Generic Name
Brand name
Adult Dosing
Approval Date
Enfuvirtide
Fuzeon
90 mg SC BID
2003
Mechanism of Action:
Binds to the gp41 subunit of the viral envelope glycoprotein, preventing the conformational changes required for the fusion of the viral and cellular membranes
Adverse effects:
Injection site reactions
Hypersensitivity
Increase risk of bacterial pneumonia

30. Ccr5 receptor antagonist
Generic Name
Brand name
Adult Dosing
Approval Date
Maraviroc
Selzentry
300mg BID
150mg BID in combination with 3A4 inhibitors
600mg BID in combination with 3A4 inducers
2007
Mechanism of Action:
Binds to CCR5 protein on CD4 cell to prevent binding
Adverse effects
Hepatotoxicity
Coughing
Dizziness
GI effects
Requires a tropism test to detect presence of CCR5 tropic virus prior use

31. Problems with antiretrovirals
Resistance
Genotyping:
Genotypic assays detect drug0resistance mutations present in the virus genes
The test is quick and result will be available within 1-2 weeks
Phenotyping:
Phenotypic assays measure the ability of a virus to grow in different concentrations of antiretroviral drugs

32. prevention Use a condom every time you have sex
If you inject drugs, don’t share needles or syringes
Don’t share razor, toothbrush, or other items that may have blood on them
Take anti-HIV medications according to healthcare provider’s directions
Infected mother with HIV should not breastfeed baby

34. References
ELISA Tests. (2005, October 1). Retrieved October 15, 2013, from MedicineNet.com:
Fauci A.S., Lane H.C. (2012). Chapter 189. Human Immunodeficiency Virus Disease: AIDS and Related Disorders. In D.L. Longo, A.S. Fauci, D.L. Kasper, S.L. Hauser, J.L. Jameson, J. Loscalzo (Eds), Harrison's Principles of Internal Medicine, 18e. Retrieved October 23, 2013 from
HIV/AIDS. (2009, March 25). Retrieved October 14, 2013, from National Institute of Allergy and Infectious Disease:
HIV in the United States: At a Glance. (2013, April 23). Retrieved October 15, 2013, from Centers for Disease Control and Prevention:
HIV Type 2. (n.d.). Retrieved October 15, 2013, from The New Yourk City Department of Health and Mental Hygiene:
Jeffrey, D., & Steven, D. e. (2013, July 13). Rappid Testing for HIV. Retrieved October 16, 2013, from Medscape:
Longo DL, Fauci AS, et al: Harrison’s Principles of Internal Medicine, 18th Edition:
Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the
prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Available at Accessed (October 16, 2013)[Table 2]
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available athttp://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf.[October 16, 2013] [B-1]
Testing for HIV. (2012, August). Retrieved October 2013, from AIDSinfo: