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Human Immunodeficiency Virus: An Overview. Elizabeth W. Delamater, Ph.D. Manager, Microbiological Sciences Division Laboratory Services Section Texas Department of State Health Services. HIV-1. HTLV-I. HIV-2. HTLV-II. (SIV). (STLV-I). Common Ancestor. Transforming Viruses

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human immunodeficiency virus an overview

Human Immunodeficiency Virus: An Overview

Elizabeth W. Delamater, Ph.D.

Manager, Microbiological Sciences Division

Laboratory Services Section

Texas Department of State Health Services

slide2

HIV-1

HTLV-I

HIV-2

HTLV-II

(SIV)

(STLV-I)

Common Ancestor

Transforming Viruses

Cell Proliferation

Cytopathic Viruses

Cell Death

human retroviruses nomenclature
Human Retroviruses - Nomenclature
  • Human Immunodeficiency Viruses
    • HIV-1 (1983)
      • HIV, HTLV III, LAV, ARV
        • AIDS and related conditions
    • HIV-2 (1986)
      • LAV-2, HTLV IV
        • AIDS (primarily in West Africa)
human retrovirus characteristics
Human Retrovirus – Characteristics
  • RNA Tumor (transforming) and immunodeficiency (cytopathic) viruses
  • Reverse Transcriptase
  • Integration of the viral genome into the host DNA as a provirus
  • Primarily infect T-lymphocytes and some neural cells
  • Exogenous (transmisssible, infectious agents)
  • Latency (long incubation period)
brief history of retroviruses
Brief History of Retroviruses
  • Transmissible agents capable of causing leukemias and solid-tissue tumors were discovered
    • 1970 – Reverse transcriptase was discovered
    • 1980 – HTLV-I and HTLV-II were isolated
    • 1981 – First AIDS case was discovered
    • 1983 – HIV-1 was isolated
    • 1985 – EIA test for anti-HIV-1 antibodies was licensed by the FDA
where did hiv come from
Where did HIV come from?
  • Estimated origin around 1930.
  • Estimated origin in Africa.
  • Thought to come from SIV in primates (blood exposure)
  • Change in travel and social norms caused the world wide epidemic.
hiv subtypes
HIV Subtypes
  • HIV isolates are classified into three different groups
    • Major group (M)
    • Outlier group (O)
    • Non-M / non-O (N)
  • Groups N and O restricted to West Africa
  • Based on the analysis of the envelope gene, there are at least nine pure subtypes or clades A-D, F-H, J and K
hiv transmission
HIV Transmission

Requires:

1) Infected body fluid.

2) Entry into the body.

Blood, Semen, Vaginal Secretions & Breast Milk

Mucous Membrane--Anal, Oral or Vaginal Sex

Blood to Blood--Needle or Broken Skin

Perinatal- In utero, During birth, Breastfeeding

routes of transmission of hiv
Sexual

Exposure to

blood

Perinatal

Homosexual between men

Heterosexual from men to women and women to men

Drug user needle sharing

Transfusion of blood, plasma

Occupational needlestick injury and other blood exposures

During pregnancy, intrapartum and postpartum (via breastfeeding)

Routes of Transmission of HIV
perinatal transmission
Perinatal transmission
  • Greatly reduced due to use of antiretroviral therapy during pregnancy
    • decrease from 24 to 8% vertical transmission with AZT
  • Trials using high doses of new antiretrovirals during labor and to newborn--success of Nevirapine
  • Women with higher viral loads more likely to transmit
slide16

Factors Affecting Transmission

STD Co-infection More likely to become infected More likely to transmit infection

Viral Load Stage of infection Treatment

disease progression
Disease Progression
  • Infection
  • Primary Infection/Antibody Development
  • Asymptomatic Period (10-12 yrs average)
  • AIDS (Opportunistic infections, CD4 200 or below)
slide19
AIDS

HIV infected + immune system breakdown

(CD4 count < 200 or AIDS Defining illness)

AIDS Defining Illnesses

Pnuemocystis pnuemonia

Toxoplasmosis

Kaposi’s sarcoma

Mycobacterium avium complex

Invasive cervical cancer

etc...

slide20

Antiretroviral Treatment

Triple Drug Cocktail--Attack the virus at different points in the replication process

  • Difficult Drug Regimens
  • Importance of Adherence
  • Side Effects
  • Expensive
slide22

Other Treatment

Prophylaxis for Opportunistic Infections

Treatment of Opportunistic Infections

Vaccines (future)

Immune Therapy

Alternative Treatment

difficulties in treatment
Difficulties in Treatment
  • Access to Care
  • Family Care Burdens
  • Language Barriers
  • Fragmentation of Care
  • Fears / Myths About Medical Care
post exposure prophylaxis
Post Exposure Prophylaxis
  • Treatment with antiretroviral drugs after an exposure to HIV.
  • Must be started within 72 hours (sooner the better) and continued for a month.
  • PEP showed a 80% reduction in HIV infections for occupational exposures.
  • Concerns for drug and sexual exposures
slide25

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

Estimated Number of AIDS Cases, Deaths, and

Persons Living with AIDS,1985-2004, United States

450

90

AIDS

1993 definition

implementation

400

Deaths

80

Prevalence

350

70

300

60

No. of cases and deaths (in thousands)

250

50

Prevalence (in thousands)

200

40

150

30

20

100

10

50

0

0

Year of diagnosis or death

Note. Data adjusted for reporting delays.

slide26

Awareness of HIV Status among

Persons with HIV, United States

Number HIV infected 1,039,000 – 1,185,000

Number unaware of

their HIV infection 252,000 - 312,000 (24%-27%)

Estimated new infections 40,000

annually

Glynn M, Rhodes P. 2005 HIV Prevention Conference

awareness of serostatus among people with hiv and estimates of transmission
Awareness of Serostatus Among People with HIV and Estimates of Transmission

~25% Unaware of Infection

Accounting for:

~54% of New Infections

Marks, et al

AIDS 2006;20:1447-50

~75% Aware of Infection

~46% of New Infections

People Living with HIV/AIDS: 1,039,000-1,185,000

New Sexual Infections Each Year: ~32,000

slide28

HIV/AIDS Diagnoses among Adults and Adolescents, by Transmission Category — 33 States, 2001–2004

MSM/IDU 5%

Other 1%

Other 3%

Heterosexual

17%

IDU

21%

MSM

61%

IDU

16%

Heterosexual

76%

Females

(n ≈ 45,000)

Males

(n ≈ 112,000)

MMWR, Nov 18, 2005

slide31
USA
  • Numbers of AIDS deaths are falling
  • Number of AIDS diagnosis are falling
  • Rates of HIV infection have NOT changed
  • Trends
    • Younger People (25% under age 25)
    • Low Socioeconomic Status
    • IDU
    • Disease of the Marginalized
knowing you are infected
Knowing You Are Infected:
  • Primary Infection
      • 2-6 wks average
      • 75 -90% have symptoms
  • Only way to know for sure: HIV Antibody Test

“Window Period”: time to develop antibodies

      • 3-6 weeks 85%
      • 3 months >99%
testing technology
Technologies

More accurate serum EIA

Oral fluids test

Home test system

Rapid test

Urine test

Strategies

Phone results

Augmented counseling

Outreach

Bars, coffee shops, bath houses

Syringe exchanges

Street (vans)

Testing Technology
tdh hiv 1 testing algorithm
TDH HIV-1 Testing Algorithm

Patient Specimen – EIA Screen

Nonreactive

Reactive

Repeat screen 2X

No further

Testing

Report as

Nonreactive

Reactive

Nonreactive

Nonreactive 2X

Reactive 2X

No further

Testing

Report as

Nonreactive

Western Blot Confirmation

Reactive

Indeterminate

Nonreactive

Retest

8 weeks

Report Reactive

Report Nonreactive

eia or elisa advantages
EIA or ELISAAdvantages
  • Simple
  • Sensitive
  • Rapid
  • Can be Automated
  • Suitable for High Volume Testing
eia or elisa limitations
EIA or ELISALimitations
  • Potential for False Positives
  • Initial High Reactives must be Repeated
slide39

Plate with Antigen coated wells

Add patient serum sample containing anti-HIV-1 antibodies

Wash, add enzyme conjugated anti-human antibodies

slide40

Wash, add appropriate substrate for the conjugated enzyme

Enzyme acts on substrate, causing a color change

types of specimens for testing1
Types of Specimens for Testing

Serum or Plasma

Dried Blood Spots

types of specimens for testing2
Types of Specimens for Testing

Serum or Plasma

Dried Blood Spots

Oral Fluid

types of specimens for testing3
Types of Specimens for Testing

Serum or Plasma

Dried Blood Spots

Oral Fluid

Urine

hiv confirmation

HIV Confirmation

Western Blot

Immunofluorescent Assay

Laboratory Only

slide54

gp160

gp120

p66

gp41

p24

p17

what about hiv 2

What about HIV-2?

Not common in the United States

Only about 72 cases confirmed as of 2000

slide57

gp160

gp120

gp41

HIV-2 confirmed by the CDC

public health need for rapid hiv tests
Public Health Need for Rapid HIV Tests
  • High rates of non-return for test results
    • In 2000, 31% did not return for results of HIV-positive conventional tests at publicly funded sites
  • Need for immediate information or referral for treatment choices
    • Perinatal settings
    • Post-exposure treatment settings
  • Screening in high-volume, high-prevalence settings
slide60

Multispot HIV-1/HIV-2

Uni-Gold Recombigen

Reveal G2

OraQuick Advance

four fda approved rapid hiv tests
Four FDA-approved Rapid HIV Tests

Sensitivity

(95% C.I.)

Specificity

(95% C.I.)

OraQuick Advance

- whole blood

- oral fluid

- plasma

99.6 (98.5 - 99.9)

99.3(98.4 - 99.7)

99.6 (98.5 - 99.9)

100(99.7-100)

99.8(99.6 – 99.9)

99.9(99.6 – 99.9)

Uni-Gold Recombigen

- whole blood

- serum/plasma

100(99.5 – 100)

100 (99.5 – 100)

99.7(99.0 – 100)

99.8 (99.3 – 100)

four fda approved rapid hiv tests1
Four FDA-approved Rapid HIV Tests

Sensitivity

(95% C.I.)

Specificity

(95% C.I.)

Reveal G2

serum

plasma

99.8(99.2 – 100)

99.8(99.0 – 100)

99.1 (98.8 – 99.4)

98.6 (98.4 – 98.8)

Multispot

serum/plasma

HIV-2

100 (99.9 – 100)

100 (99.7 – 100)

99.9 (99.8 – 100)

revised recommendations adults and adolescents i
Revised RecommendationsAdults and Adolescents - I
  • Routine, voluntary HIV screening for all persons 13-64 in health care settings, not based on risk
  • Repeat HIV screening of persons with known risk at least annually
  • Opt-out HIV screening with the opportunity to ask questions and the option to decline
  • Include HIV consent with general consent for care; separate signed informed consent not recommended
  • Prevention counseling in conjunctions with HIV screening in health care settings is not required
opt out screening
Opt-Out Screening

Prenatal HIV testing for pregnant women:

  • RCT of 4 counseling models with opt-in consent:
    • 35% accepted testing
    • Some women felt accepting an HIV test indicated high risk behavior
  • Testing offered as routine, opportunity to decline
    • 88% accepted testing
    • Significantly less anxious about testing

Simpson W, et al, BMJ June,1999

routine opt out hiv testing texas std clinics 1996 97
Routine Opt-Out HIV TestingTexas STD Clinics, 1996-97

Opt-In Opt-Out

N (%) N (%) % change

STD Visits 31,558 34,533 +9 Eligible Clients 19,184 (61) 23,686 (69) +23

Pre-test counsel 15,038 (78) 11,466 (48) -24

Tested 14,927 (78) 23,020 (97) +54

Post-test counsel 6,014 (40) 4,406 (19) -27

HIV-positive 168 (1.1) 268 (1.2) +59

Texas Department of State Health Services, 2005

revised recommendations adults and adolescents ii
Revised RecommendationsAdults and Adolescents - II
  • Intended for all health care settings, including inpatient services, EDs, urgent care clinics, STD clinics, TB clinics, public health clinics, community clinics, substance abuse treatment centers, correctional health facilities, primary care settings
  • Communicate test results in same manner as other diagnostic/screening tests
  • Provide clinical HIV care or establish reliable referral to qualified providers
revised recommendations adults and adolescents iii
Revised RecommendationsAdults and Adolescents - III
  • Low prevalence settings:
    • Initiate screening
    • If yield from screening is less than 1 per 1000, continued screening is not warranted
  • Steps should be considered to resolve conflicts between the recommendations and state or local regulations
revised recommendations pregnant women i
Revised RecommendationsPregnant Women - I
  • Universal opt-out HIV screening
    • Include HIV in routine panel of prenatal screening tests
    • Consent for prenatal care includes HIV testing
    • Notification and option to decline
  • Second test in 3rd trimester for pregnant women:
    • Known to be at risk for HIV
    • In jurisdictions with elevated HIV incidence
    • In high HIV prevalence health care facilities
revised recommendations pregnant women ii
Revised RecommendationsPregnant Women - II
  • Opt-out rapid testing with option to decline for women with undocumented HIV status in L&D
    • Initiate ARV prophylaxis on basis of rapid test result
  • Rapid testing of newborn recommended if mother’s status unknown at delivery
    • Initiate ARV prophylaxis within 12 hours of birth on basis of rapid test result
summary
Summary
  • There is an urgent need to increase the proportion of persons who are aware of their HIV-infection status
  • Expanded, routine, voluntary, opt-out screening in health care settings is needed
  • Such screening is cost-effective
  • Recommendations Revised: September 2006
  • Several jurisdictions have already begun
key messages
Key Messages
  • The large majority of people with HIV continue to be men who have sex with men. People of color are disproportionately represented among new infections
  • The basic modes of transmission and prevention of HIV have not changed in 20 years
  • The AIDS epidemic is not over, but there is more hope than ever for those that are infected