Transcript CASES REPORTED 1999

OBJECTIVES
EPIDIMIOLOGY
 Concentrate on Obstetrics and Gynecology
 The virus
CLINICAL FEATURES
SCREENING + DIAGNOSTIC TESTS
HIV in Obstetrics Population
 To screen or Not to screen.
1
Cont.
OBJECTIVES
PRE- + POST TEST COUNSELLING
PERINATAL TRANSMISSION
VIRAL LOAD + PERINATAL TRANSMISSION
2
Cont.
OBJECTIVES
MANAGEMENT OF OBSTETRICS PATIENT WITH
AIDS
 Reduction of perinatal transmission
 Vaccination
 Drug therapy for AIDS related infection
 Delivering AID patient
3
CASES REPORTED 1999
TOTAL
: 5.6 MILLION
MALES
: 2.7 MILLION
FEMALES : 2.3 MILLION
CHILDREN : 570 HUNDRED THOUSAND
 90% OF THESE ARE PERINATAL TRANSMISSION
4
NUMBER OF DEATHS 1999
TOTAL
: 2.6 MILLION
MALES
: 1 MILLION
FEMALES : 1.1 MILLION
CHILDREN : 470 HUNDRED THOUSAND
5
NUMBER OF AIDS 1999
TOTAL
: 33.6 MILLION
MALES
: 17.6 MILLION
FEMALES : 14.8 MILLION
CHILDREN : 1.2 MILLION
6
NUMBER OF AIDS 2000
TOTAL
: 34.7 MILLION
MALES
: 18.3 MILLION
FEMALES : 16.4 MILLION
7
NUMBER OF DEATHS UNTIL 1999
TOTAL
: 16.3 MILLION
MALES
:
FEMALES :
CHILDREN :
6.5 MILLION
6.2 MILLION
3.6 MILLION
8
ETIOLOGY
RNA
TYPE I
TYPE II
: RETROVUS
: COMMENTIST
: MORE COMMON IN
WEST AFRICA
9
1981
1983
1984
-
Internal case
Virus disease
Antibodies tests developed
(Cumulative cases)
10
PATHOLOGY
TARGET CELLS
 CD4 Helper lymphocytes (Primary Target)
 Macrophages
CNS
 Placenta
SUPRESS IMMUNITY
INCREASE SUSCEPTIBILITY TO OPPORTUNISTIC
INFECTIONS AND NEOPLASMS
11
I am an Obstetrician not an
Internist, why should I be
HIV oriented?
12
14% of HIV infected patients are women.
HIV is the third leading cause of women age
25-44 years ( in USA)
Prevalence of HIV infected pregnant women is
16:1000
90% of HIV infection in children worldwide is
related to perinatal transmission of the virus.
85% of AIDS cases in women between ages
15-44 years.
13
CLINICAL FEATURES
At the time of exposure
 asymptomatic
 acute mild syndrome similar to mononucleosis
Latest Period (Window Phase)
(Seroconvertion)
Viral isolation - Antigen (PCR)
14
Immune dysfunction phase wide range of clinical
condition
 P.U.O.
 Weight loss
 Lymphadenopathy
 CNS dysfunction
 Abnormal Pap tests
 Recurrent C.I.N.
 Recurrent oral and vaginal candidiasis
15
CLASSIFICATION OF THE DISEASE
16
SEROCONVERTION ILLNESS
17
SCREENING TEST
To detect antibodies to the virus rather that the
virus itself
ELISA – 3 weeks-3 months to appear
18
CONFIRMATORY TEST
WESTERN BLOT ASSAY
 Sensitivity and specificity are more than
99%
 Repeating the test will eliminate the false
positive result.
19
TO SCREEN OR NOT TO SCREEN?
The best defense is a strong offense.
The American Academy of Paediatrics and the
ACOG issued a Joint Statement on HIV Screening
in Pregnancy (1995).
A pregnant women should receive HIV counseling
as part of their routine ANC.
A pregnant women should have HIV testing with
their consent.
20
PRE-TEST COUNSELING
Risks of transmission (including Mode)
Risks of perinatal transmission
Potential social and psychological implication of
Positive test.
The availability of Agents that may reduce the risk
of neonatal infection.
Clarify the difference between HIV infection and
disease.
21
POST-TEST COUNSELING
NEGATIVE Test in High Risk
Patient should be informed about
false Negative Results related to the
latest period.
22
PATIENT WITH POSITIVE TEST
Description of early clinical manifestation of HIV
infection.
Current understanding of the prognosis.
Risk of Perinatal transmission.
Prohibition from blood donation.
Not to share instrument that may be exposed to
blood, like toothbrush.
23
Cont.
PATIENT WITH POSITIVE TEST
Testing for the partner.
Psychological and emotional support
Discuss the strategies available to maintain
better quality of life.
Emphasis the importance of follow up.
24
PERINATAL TRANSMISSION
In the absence of treatment, the risk of
Perinatal transmission is 13-40%.
Time of transmission - not certain yet.
? 50% during labor and delivery.
25
FACTORS ASSOCIATED WITH INCREASE
RISK OF PERINATAL TRANSMISSION.
Low CD4 count.
Scalp electrode – scalp sampling.
Prolonged rupture of membrane.
Viral blood
26
FOLLOW UP
CD4 Count (Monthly)
Viral blood were viral RNA Quantitative
measures are available.
27
REDUCTION OF PERINATAL
TRANSMISSION
Multicenter trial
- N. Eng. J 1994
 Showed reduction of rate of Perinatal
Transmission from 25% - 8% using ZDV
between 14-34 weeks.
 No increasing in the congenital anomalies.
 No major side effect.
28
DELIVERY
No evidence to support C/S to reduce
the risk of infection.
A R M , scalp electrode, fetal scalp
sampling should be avoided.
29
POSTPARTUM
•
AVOID BREAST FEEDING
Risk  by 10-20 %
30
PROVISIONAL PUBLIC HEALTH SERVICE
RECOMMENDATION FOR CHEMO PROPHYLAXIS
AFTER HIV EXPOSURE (1996)
PERCUTANEOUS EXPOSURE
 HIGH RISK
 Large volume of blood (deep injury with
large diameter load exposed to HIV
positive patient
 RECOMMEND AZT
 Acute viral illness – AIDS, High Viral Load
 RECOMMEND AZT
31
 NO HIGH RISK
 Exposure to liquids and secretion that are
potentially infection.
 OFFER AZT
32
MUCOSAL EXPOSURE
 Blood Offer
 Fluid contaminated – not offer
SKIN EXPOSURE
 Blood offer
 Other fluid - not offer
33
PRECAUTIONS:
Double gloving
Eye coverage at delivery
Avoid mouth suction in resuscitating the neonates
Careful handling of needles + sharps
Use closed vacuum collection system for blood with
___________.
34
WHEN THE HIV TEST IS POSITIVE
Check the following:
 General Health Status
 Past Medical History
- General well being
- Constitutional symptoms
- Nutritional assessment
- Gynecologic/obstetrical history:
menstrual irregularity, previous
abnormal Pap smears
- Receipt of blood transfusions or
other blood products
35
 Drug History
- Medication: prescription and
non-prescription
- Complementary therapies
- Recreational use: smoking,
alcohol, injection drug use
including steroids, and street
drugs
36
 SEXUAL HISTORY -
STDs
Sexual activities
Previous sexual partners
Current sexual partners
Current sexual practices
Partners at risk
Method of contraception
37
Risks of Infectious Complications
 Immunizations
 Travel history
 Previous countries of residence
 Country of origin
 Occupational history
 Personal and family history of TB
 Previous PPD results
 Personal and family history of hepatitis B & C 38
Psychosocial History
Education
 Social supports
 Financial and employment
background

39
REVIEW OF SYSTEMS - GENERAL
Constitutional symptoms of :
 Fatigue
 Fever
 Sweats and night sweats
 Loss of appetite and weight
Skin/Mucous Membranes
 Lesions
 Rashes
 Bruising
 Ulcers
 Pain/tenderness
40
Respiratory
 Upper: nasal and sinus congestion and pain
 Lower: cough, sputum, shortness of breath,
chest pain.
Gastrointestinal
- Taste
- Nausea
- Vomiting
- Diarrhea
- Hepatitis
-
Dysphagia
Vomiting
Abdominal & rectal pain
Jaundice
41
Genitourinary
 Dysuria
 Discharges
 Pelvic pain
Neurologic System
 Central: cognitive, memory, personality, seizures,
weakness/pain/tingling/balance, visual
changes
 Peripheral: weakness/pain/tingling in extremities
42
Psychiatric
 Mood
 Libido
 Cognitive
 Concentration
 Thought content
 Sleep
43
BASELINE LABORATORY INVESTIGATION
The Minimum Baseline tests are:











Chest X-ray
CBC and differential, smear, platelets
B12 and Folic acid
BUN and Creatinine, liver function, electrolytes
Pap smear for women
Appropriate swabs for STDs, syphilis serology
TB skin test
Hepatitis B and C screening
Toxoplasmosis titre
Absolute CD4, % CD4 of total lymphocytes
CMV IgG Serology
44
BASELINE PHYSICAL EXAMINATION
Check the following:
 Weight, Temperature, and Vital Signs
 Head and Neck
- Oral lesions
- Sinus tenderness
- Nasal congestion
 Lymph nodes
- Cervical
- Supraclavicular
- Axillary
- Inguinal
45
Cont.
Baseline Physical Examination
Chest and Cardiovascular Abdominal and Rectal
-
Air entry
Adventitial sounds
Murmurs
Tachycardia
Hepatosplenomegaly
Abdominal tenderness
Rectal lesions
46
Cont.
Baseline Physical Examination
Genito-urinary
- Discharge
- Genital lesions
Pelvic
- Vaginal discharge
- Cervical lesions
- Pelvic and adnexal
mass and tenderness
47
Cont.
Baseline Physical Examination
Neurologic
Mental Status
Skin
-
Fundoscopic and visual field changes
Focal motor/sensory signs
Mood/affect
Cognitive/perceptive
Memory/judgment/insight
Rashes
Ulcers
Lesions, including Kaposi’s
sarcoma (KS)
48
TRANSMISSION OF THE VIRUS
Sexual intercourse
 anal and vaginal
Contaminated needles
 Intravenous drug users
 needlestick injuries
 injections
49
Mother  child
in utero
 at birth
 breast milk

Organ/tissue donation
 Semen
 Kidneys
 Skin, bone marrow, corneas, heart valves,
tendons, etc.
50
HIV Transmission: Global Summary
Type of exposure
% of Global Total
a) Blood Transfusion
3–5
b) Perinatal
5 – 10
c) Sexual intercourse
70 – 80
(Vaginal)
(60 – 70)
( Anal)
( 5 – 10)
d) Injecting drug use (sharing needles, etc) 5 – 10
e) Health care (needlestick injury, etc)
<0-0151
Cumulative AIDS cases reported to the
World Health Organization, June 1996
The Americas
Europe
Africa
Oceania
Asia
-
690,042
167,578
499,037
7,285
___29,707___
TOTAL
-
1,393,649
52
For women with CD4 counts above 500 cells/mm3:
 Cervicovaginal cytology (Pap smear) six months x 2,
if adequate and negative, then annually
 If Pap smear is positive for the presence of HPV, with
koilocytes or condyloma:
 Three-monthly Pap smear
 Six-monthly colposcopic acetic acid
examination
53
For women with CD4 counts from 200 to 500
cells/mm3:
 Six-monthly Pap smear
 Baseline colsposcopic examination using
acetic acid visualization, to be repeated
annually if Pap smear is negative, or sixmonthly if the presence of HPV is detected.
54
For women with CD4 counts under 200 cells/mm3:
 Three-monthly Pap smear
 Colposcopic examination using acetic acid
visualization, to be repeated six-monthly
55
First Aid and Inoculation Injuries
FIRST AID
 Body fluids on skin, in eyes, or in mouth
 Wash away immediately
 Penetrating wounds
 Encourage bleeding
 Wash with soap and water
 Report to supervisor and medical officer
56
ZIDOVUDINE THERAPY
ANTEPARTUM
Oral administration of 100mg of Zidovudine (ZDV)
five times daily, initiated as soon as possible beyond
14 weeks of gestation and continued throughout the
pregnancy.
LABOR AND DELIVERY
 During labor, intravenous administration of ZDV in a
1-hour loading dose of 2mg/kg of body weight,
followed by a continuous infusion of 1 mg/kg of body
weight per hour until delivery.
57
Cont.
ZIDOVUDINE THERAPY
NEONATAL
Oral administration of ZDV to the newborn (ZDV
syrup at 2mg/kg of body weight per dose every 6
hours) for the first 6 weeks of life, beginning
8-12 hours after birth.
58
RISKS TO HEALTH WORKER
Needle stick. Risk is .32% or 32:1000
Mucous membranes – Percutaneous exposure
to infected blood.
0.03% or 3:1000
No evidence that the virus is spread by
mosquitoes, lice, bed bugs, swimming pools,
sharing cups or eating and cooking utensils,
toilets.
59
FIRST AID MANAGEMENT
TO EXPOSURE
TESTING ___________
 Repeat in 6weeks – 3 months - - - 6 months
 Test for other blood born infection
 Hepatitis B & C – risk may _______ 30%.
PROPHYLACTIC USE OF AZT
60
RISK OF BLOOD TRANSFUSION
HEPATITIS
HIV
-
1: 100,000
1: 500,000
61
HIV IN GYNECOLOGICAL PATIENT
STD
Recurrent candida infection refractory to
conventional treatment.
Recurrent cervical dysplasia - cervical ca.
 Recommend follow up in HIV positive.
62
Maternal Viral Load (VL), ZDV Treatment and
the Risk of Perinatal HIV Transmission
Correlation between high maternal VL and transmission
Transmission observed at every VL level, including
undetectable levels
No HIV RNA threshold below which there was no risk of
transmission.
ZDV decreases transmission regardless of HIV RNA
level
Recommendation: Initiate maternal ZDV regardless of
plasma HIV RNA or CD4 counts.
63
Changing HIV Therapy During Pregnancy
Poor CD4 response
Drugs with potential teratogenicity
Poor viral load response
Poor adherence to regimen
Evidence of viral resistance
64
Follow-Up Assessment of
Pregnant Woman with HIV
4 weeks after initiation of treatment, then every
3 months if viral load stable
Fetal assessment based on gestational age
 CD4+ and viral load response
 New onset of symptoms
 Side effects or toxicities
 Adherence to therapy
 Long-range planning for continuity of medical
care
65

CLINICAL SCENARIO 3
Women with HIV infection and present in labor with no previous
treatment:
 Discuss benefits of treatment during intrapartum and
neonatal period
 Four treatment options
 Single dose Nevirapine for mother at onset of labor followed by single dose of
Nevirapine for the newborn at age 48–72 hours.
 Oral ZDV/3TC for mother during labor followed by one week oral ZDV/3TC to the
newborn
 Intrapartum IV ZDV followed by six weeks ZDV for the newborn
 The two-dose Nevirapine regimen as above combined with intrapartum IV66ZDV
and six week ZDV for the newborn.
CLINICAL SCENARIO 2
Women currently on antiretroviral therapy:
 Discuss benefits and potential risks of her current regiment
during pregnancy
 Add or substitute ZDV at 14 weeks
 Recommend intrapartum and neonatal ZDV
 Discontinue teratogenic drugs
 Consider continuing or stopping current therapy based on
gestational age (<14 weeks).
 If therapy is stopped, stop and restart all ARV simultaneously
 Resistance testing for suboptimal viral suppression or failure.
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Guidelines for Antiretroviral Drugs
in Pregnancy: Clinical Scenario 1
Women without prior antiretroviral therapy:
 Recommend:
• Standard combination therapy for women with high viral load, low
CD4 count
• Combination therapy for women with viral load 1000 regardless
of clinical or immunologic status
• 3-part ZDV regimen to reduce perinatal transmission for all HIVinfected pregnant women, regardless of antenatal viral load
 Consider delaying therapy until completion of first
trimester.
 Offer scheduled cesarean delivery for women with viral
loads >1000 (based on most recent VL results).
68
WHEN SHOULD AN ADULT BE TREATED?
Clinical Category
CD4+ count & HIV RNA
Recommendations
Symptomatic
Any value
Treat
--------------------------------------------------------------------------------------------------Asymptomatic
CD4+ T cells <200/mm3
Treat
HIV RNA – any value
-----------------------------------------------------------------------CD4+ T cells >200/mm3 but
Offer treatment if pt
<350/mm3, HIV RNA any value
willing to accept
-------------------------------------------------------------------------------------------------Asymptomatic
CD4+ T cells >350/mm3, HIV
Some experts would
RNA >30,000 (bDNA) or
treat
>55,000 (RT-PCR)
----------------------------------------------------------------------CD4+ T cells >350/mm3, HIV
Many experts would
RNA <30,000 (bDNA) or <55,000 delay therapy &
69
(RT-PCR)
observe
Reducing HIV Transmission
with Suboptimal Regimens
Partial ZDV regimens: ( New York cohort)
 Transmission rates
• 6.1% with prenatal, intrapartum, and infant ZDV
-------------------------------------------------------------------• 10% with only intrapartum ZDV
• 9.3% if only infant ZDV started within first 48 hours
• 26.6% with no ZDV
70
Reducing Intrapartum HIV Transmission:
Studies of Short Course Therapy
Oral ZDV in a non-breastfeeding population (Thailand)
from 36 weeks and during labor
 Transmission rate: 9.4% ZDV vs. 18.9% placebo
PETRA study – intrapartum/postpartum oral ZDV/3TC in a
breast-feeding population (Uganda, S. Africa, Tanzania)
 Transmission rate: 10% ZDV/3TC vs. 17% placebo
HIVNet 012 – intrapartum/postpartum/neonatal Nevirapine
(NVP) vs. short course/neonatal ZDV in a breast-feeding
population (Uganda)
 Transmission rate: 12% NVP vs. 21% ZDV
71
Follow-Up of Uninfected Infants in ZDV
versus Placebo
No significant difference in growth
No difference in CD4 and CD8 counts between
groups
No other safety abnormalities have been identified
No differences in Bayley developmental scores in
uninfected infants.
72
Maternal Viral Load and Risk of Transmission
(Women & Infants Transmission Study (WITS) )
HIV – 1 RNA
<1000
1000 – 10,000
10,001 – 50,000
50,001 - 100,000
>100,000
Transmission %
0
16.6
21.3
30.9
40.6
N
0/57
32/193
39/183
17/54
26/64
73
Factors Influencing Perinatal Transmission
Maternal Factors





HIV-1 RNA levels (viral load)
Low CD4 lymphocyte count
Other infections, Hepatitis C, CMV, bacterial vaginosis
Maternal infection drug use
Lack of ZDV during pregnancy
Obstetrical Factors
 Length of ruptured membranes/chorioamnionitis
 Vaginal delivery
 Invasive procedures
Infant Factors
 Prematurity
74
Timing of Perinatal HIV Transmission
Cases documented intrauterine, intrapartum, and
postpartum by breastfeeding
 In utero 25% 40% of cases
 Intrapartum- 60% 75% of cases
 Addition risk with breastfeeding
• 14% risk with established infection
• 29% risk with primary infection
 Current evidence suggests most transmission occurs
during the intrapartum period
75
National Recommendation for HIV Testing of
Pregnant Women
Universal testing with patient notification
as a routine component of prenatal care
 American Academic of Pediatrics and the
American College of Obstetricians and
Gynecologists Joint Statement 1999
76
Impact of PHS Guidelines for Reducing
Perinatal HIV Transmission
4-State Study: Louisiana, Michigan, New Jersey and South
Carolina (CDC, 1998)
1993 - 1996
 Women diagnosed before giving birth 68% 81%
 Women offered prenatal ZDV
27% 85%
 Women offered intrapartum ZDV
5% 75%
 Infants offered neonatal ZDV
5%76%
77
Scope of the Epidemic Among Women and
Children
AIDS in women has risen from 7% early in the
epidemic to 24% of adult cases today
263 new AIDS cases reported in children in 1999
10,000 – 20,000 estimated children living with HIV
infection
300 – 400 babies continue to be born with HIV
infection each year in the U.S.
78
RECOMMENDATIONS
(SOGC Infectious Disease Committee)
Elective cesarean section (38 weeks gestation) has a
valuable role for pregnant women with HIV and should
be offered in these specific situations:
1. Women who have not received antiretroviral therapy
regardless of the antepartum viral load determination.
2. Women receiving antiretroviral monotherapy regardless
of the viral load.
3. Patients with detectable viral load regardless of the
received therapy.
79
PEOPLE NEWLY INFECTED
WITH HIV IN 2001
TOTAL
5 MILLION
ADULTS
WOMEN
CHILDREN <15 YEARS
4.2 MILLION
2 MILLION
800,000
80
NUMBER OF PEOPLE LIVING WITH HIV/AIDS
As of End of 2001
TOTAL
40 MILLION
ADULTS
WOMEN
CHILDREN <15 YEARS
37.1 MILLION
18.5 MILLION
3 MILLION
81
AIDS DEATH IN 2001
TOTAL
ADULTS
WOMEN
CHILDREN <15 YEARS
3 MILLION
2.4 MILLION
1.1 MILLION
580,000
82
TOTAL NUMBER OF CHILDREN ORPHANED
BY AIDS, AND LIVING, END 2001
14 MILLION
83
PROPHYLACTIC DRUG THERAPY FOR
AID RELATED INFECTIONS
When CD4 count less that 200/mm2
 P carinii pneumonia prophylaxis should be started
 Trimethropin-Sulfamehoxazole (Bactrim-Septra)
160mg/day
 Other – Diaphenylsuphane (Dopsane) 100mg daily
 Pentamide 60mg every 2 weeks
 AZT prophylaxis should be started
84
RECURRENT CANDIDA
 Oral Ketoconazole 400mg
 Fluconazole 100mg
or
ANTI TB
 INH
or
 Rifamycin
85
IMMUNIZATION
Susceptible patients should received:
 Hepatitis B
 Pneumococcal
 Influenza vaccine
86