Human Immunodeficiency Virus: An Overview

Elizabeth W. Delamater, Ph.D.

Manager, Microbiological Sciences Division

Laboratory Services Section

Texas Department of State Health Services

Common Ancestor

(STLV-I)

HTLV-I

HTLV-II

HIV-1

HIV-2

(SIV)

Transforming Viruses

Cell Proliferation

Cytopathic Viruses

Cell Death

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

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

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?

• 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 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

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)

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

Factors Affecting Transmission

STD Co-infectionMore likely to become

infectedMore likely to transmit

infection

Viral Load Stage of infectionTreatment

Disease Progression

Infection

Primary Infection/Antibody Development

Asymptomatic Period (10-12 yrs average)

AIDS (Opportunistic infections, CD4 200 or below)

AIDS

AIDS Defining IllnessesPnuemocystis pnuemonia

ToxoplasmosisKaposi’s sarcoma

Mycobacterium avium complexInvasive cervical cancer

etc...

HIV infected + immune system breakdown

(CD4 count < 200 or AIDS Defining illness)

Antiretroviral Treatment

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

•Importance of Adherence•Side Effects•Expensive

Other Treatment

Prophylaxis for Opportunistic Infections

Treatment of Opportunistic Infections

Vaccines (future)

Alternative Treatment

Immune Therapy

Difficulties in Treatment

Access to Care Family Care Burdens Language Barriers Fragmentation of Care Fears / Myths About Medical Care

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

Estimated Number of AIDS Cases, Deaths, and Persons Living with AIDS,1985-2004, United States

Note. Data adjusted for reporting delays.

No.

of c

ases

and

dea

ths

(in th

ousa

nds)

Year of diagnosis or death

Prevalence (in thousands)

0 0

90400

450

10

20

50

30

100

40150

50

200

60

250

70

300

80350

19851986198719881989199019911992199319941995199619971998199920002001200220032004

DeathsPrevalence

AIDS 1993 definitionimplementation

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

Awareness of HIV Status among Persons with HIV, United States

Glynn M, Rhodes P. 2005 HIV Prevention Conference

Awareness of Serostatus Among People with HIV and Estimates of Transmission

~25% Unaware

of Infection

~75% Aware of Infection

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

New Sexual Infections Each Year: ~32,000

Accounting for: ~54% of New

Infections

~46% of New

Infections

Marks, et alAIDS 2006;20:1447-50

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

MSM61%IDU

16%

Heterosexual17%

MSM/IDU 5% Other 1%

Males(n ≈ 112,000)

Females(n ≈ 45,000)

Heterosexual76%

IDU21%

Other 3%

MMWR, Nov 18, 2005

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:

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)

TDH HIV-1 Testing AlgorithmPatient Specimen – EIA Screen

Nonreactive Reactive

No further

Testing

Report as

Nonreactive

Repeat screen 2X

Reactive 2XReactive

Nonreactive

Nonreactive 2X

Western Blot Confirmation No further

Testing

Report as

Nonreactive

Reactive NonreactiveIndeterminate

Report Reactive

Retest

8 weeks

Report Nonreactive

HIV Screening

Enzyme Immunoassay

EIA or ELISA

EIA or ELISAAdvantages

Simple Sensitive Rapid Can be Automated Suitable for High Volume Testing

EIA or ELISALimitations

Potential for False Positives Initial High Reactives must be Repeated

Types of Specimens for Testing

Serum or Plasma

Plate with Antigen coated wells Add patient serum sample containing anti-HIV-1 antibodies

Wash, add enzyme conjugated anti-human antibodies

Wash, add appropriate substrate for the conjugated enzyme

Enzyme acts on substrate, causing a color change

Types of Specimens for Testing

Serum or Plasma

Dried Blood Spots

Types of Specimens for Testing

Serum or Plasma

Dried Blood Spots

Oral Fluid

Types of Specimens for Testing

Serum or Plasma

Dried Blood Spots

Oral Fluid

Urine

HIV Confirmation

Western Blot

Immunofluorescent Assay

Laboratory Only

gp160

gp120

p66

gp41

p24

p17

What about HIV-2?

Not common in the United States

Only about 72 cases confirmed as of 2000

gp160gp120

gp41

HIV-2 confirmed by the CDC

HIV Rapid 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

Uni-Gold Recombigen

Multispot HIV-1/HIV-2

Reveal G2 OraQuick

Advance

Four FDA-approved Rapid HIV Tests

99.7 (99.0 – 100)

99.8 (99.3 – 100)

100 (99.5 – 100)

100 (99.5 – 100)

Uni-Gold Recombigen

- whole blood

- serum/plasma

100 (99.7-100)

99.8 (99.6 – 99.9)

99.9 (99.6 – 99.9)

99.6 (98.5 - 99.9)

99.3 (98.4 - 99.7)

99.6 (98.5 - 99.9)

OraQuick Advance

- whole blood

- oral fluid

- plasma

Specificity

(95% C.I.)

Sensitivity

(95% C.I.)

Four FDA-approved Rapid HIV Tests

99.9 (99.8 – 100)100 (99.9 – 100)

100 (99.7 – 100)

Multispot

serum/plasma

HIV-2

99.1 (98.8 – 99.4)

98.6 (98.4 – 98.8)

99.8(99.2 – 100)

99.8(99.0 – 100)

Reveal G2

serum

plasma

Specificity

(95% C.I.)

Sensitivity

(95% C.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

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 TestingTexas STD Clinics, 1996-97

Texas Department of State Health Services, 2005

Opt-In Opt-Out N (%) N (%) % change

STD Visits 31,558 34,533 +9Eligible Clients 19,184 (61) 23,686 (69) +23Pre-test counsel 15,038 (78) 11,466 (48) -24Tested 14,927 (78) 23,020 (97) +54

Post-test counsel 6,014 (40) 4,406 (19) -27HIV-positive 168 (1.1) 268 (1.2) +59

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 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 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 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

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

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