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)
Transforming Viruses
Cell Proliferation
Cytopathic Viruses
Common Ancestor
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.
Blood, Semen, Vaginal Secretions & Breast Milk
2) Entry into the body.
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
 Homosexual between men
 Heterosexual from men to
women and women to men
 Exposure to
blood
 Drug user needle sharing
 Transfusion of blood, plasma
 Occupational needlestick injury
and other blood exposures
 Perinatal
 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-infection
More likely to become infected
More likely to transmit infection
Viral Load
Stage of infection
Treatment
Disease Progression
 Infection
 Primary Infection/Antibody Development
 Asymptomatic Period (10-12 yrs average)
 AIDS (Opportunistic infections, CD4 200 or
below)
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...
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)
Immune Therapy
Alternative Treatment
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
90
80
70
AIDS
Deaths
Prevalence
1993 definition
implementation
450
400
Prevalence (in thousands)
No. of cases and deaths (in thousands)
Estimated Number of AIDS Cases, Deaths, and
Persons Living with AIDS,1985-2004, United States
350
60
50
300
250
40
200
150
30
20
100
10
0
50
1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004
Year of diagnosis or death
Note. Data adjusted for reporting delays.
0
Awareness of HIV Status among
Persons with HIV, United States
Number HIV infected
Number unaware of
their HIV infection
Estimated new infections
annually
1,039,000 – 1,185,000
252,000 - 312,000 (24%-27%)
40,000
Glynn M, Rhodes P. 2005 HIV Prevention Conference
Awareness of Serostatus Among People
with HIV and Estimates of Transmission
~25%
Unaware
of
Infection
Accounting for:
~75%
Aware of
Infection
~54%
of New
Infections
Marks, et al
AIDS 2006;20:1447-50
~46%
of New
Infections
People Living with
HIV/AIDS: 1,039,0001,185,000
New Sexual Infections
Each Year: ~32,000
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%
IDU
16%
MSM
61%
Males
(n ≈ 112,000)
MMWR, Nov 18, 2005
Heterosexual
76%
Females
(n ≈ 45,000)
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 Algorithm
Patient Specimen – EIA Screen
Nonreactive
Reactive
No further
Repeat screen 2X
Testing
Report as
Reactive 2X
Nonreactive
Reactive
Nonreactive
Western Blot Confirmation
Nonreactive
2X
No further
Testing
Reactive
Report
Reactive
Indeterminate
Retest
8 weeks
Nonreactive
Report as
Nonreactive
Report
Nonreactive
HIV Screening
Enzyme Immunoassay
EIA or ELISA
EIA or ELISA
Advantages





Simple
Sensitive
Rapid
Can be Automated
Suitable for High Volume Testing
EIA or ELISA
Limitations
 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
gp160
gp120
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
Multispot
HIV-1/HIV-2
Uni-Gold
Recombigen
Reveal
G2
OraQuick
Advance
Four FDA-approved Rapid HIV
Tests
Sensitivity
(95% C.I.)
Specificity
(95% C.I.)
OraQuick Advance
- whole blood
99.6 (98.5 - 99.9)
- oral fluid
99.3 (98.4 - 99.7)
- plasma
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
100 (99.5 – 100)
- serum/plasma 100 (99.5 – 100)
99.7 (99.0 – 100)
99.8 (99.3 – 100)
Four FDA-approved Rapid HIV
Tests
Sensitivity
(95% C.I.)
Reveal G2
serum
plasma
Specificity
(95% C.I.)
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 100 (99.9 – 100)
100 (99.7 – 100)
HIV-2
99.9 (99.8 – 100)
Revised Recommendations
Adults 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 Testing
Texas STD Clinics, 1996-97
Opt-In
N (%)
STD Visits
Eligible Clients
Pre-test counsel
Tested
Post-test counsel
HIV-positive
Opt-Out
N (%)
% change
31,558
19,184 (61)
15,038 (78)
14,927 (78)
34,533
23,686 (69)
11,466 (48)
23,020 (97)
+9
+23
-24
+54
6,014 (40)
168 (1.1)
4,406 (19)
268 (1.2)
-27
+59
Texas Department of State Health Services, 2005
Revised Recommendations
Adults 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
 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
 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
 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