OBJECTIVES

1
OBJECTIVES

• EPIDIMIOLOGY
• Concentrate on Obstetrics and Gynecology
• The virus
• CLINICAL FEATURES
• SCREENING DIAGNOSTIC TESTS
• HIV in Obstetrics Population
• To screen or Not to screen.

2
Cont. OBJECTIVES

• PRE- POST TEST COUNSELLING
• PERINATAL TRANSMISSION
• VIRAL LOAD PERINATAL TRANSMISSION

3
Cont. OBJECTIVES

• MANAGEMENT OF OBSTETRICS PATIENT WITH AIDS
• Reduction of perinatal transmission
• Vaccination
• Drug therapy for AIDS related infection
• Delivering AID patient

4
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

5
NUMBER OF DEATHS 1999

• TOTAL 2.6 MILLION
• MALES 1 MILLION
• FEMALES 1.1 MILLION
• CHILDREN 470 HUNDRED THOUSAND

6
NUMBER OF AIDS 1999

• TOTAL 33.6 MILLION
• MALES 17.6 MILLION
• FEMALES 14.8 MILLION
• CHILDREN 1.2 MILLION

7
NUMBER OF AIDS 2000

• TOTAL 34.7 MILLION
• MALES 18.3 MILLION
• FEMALES 16.4 MILLION

8
NUMBER OF DEATHS UNTIL 1999

• TOTAL 16.3 MILLION
• MALES 6.5 MILLION
• FEMALES 6.2 MILLION
• CHILDREN 3.6 MILLION

9
ETIOLOGY

• R N A RETROVUS
• TYPE I COMMENTIST
• TYPE II MORE COMMON IN
• WEST AFRICA

10

• 1981 - Internal case
• 1983 - Virus disease
• 1984 - Antibodies tests developed
• (Cumulative cases)

11
PATHOLOGY

• TARGET CELLS
• ? CD4 Helper lymphocytes (Primary Target)
• ? Macrophages
• ? C N S
• ? Placenta
• SUPRESS IMMUNITY
• INCREASE SUSCEPTIBILITY TO OPPORTUNISTIC
• INFECTIONS AND NEOPLASMS

12

• I am an Obstetrician not an Internist, why should
  I be
• HIV oriented?

13

• 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
  161000
• 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.

14
CLINICAL FEATURES

• At the time of exposure
• ? asymptomatic
• ? acute mild syndrome similar to
  mononucleosis
• Latest Period (Window Phase)
• (Seroconvertion)
• Viral isolation - Antigen (PCR)

15

• 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

16
CLASSIFICATION OF THE DISEASE
17
SEROCONVERTION ILLNESS
18
SCREENING TEST

• To detect antibodies to the virus rather that the
  virus itself
• ELISA 3 weeks-3 months to appear

19
CONFIRMATORY TEST

• WESTERN BLOT ASSAY
• ? Sensitivity and specificity are more
  than
• 99
• ? Repeating the test will eliminate the
  false
• positive result.

20
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.

21
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.

22
POST-TEST COUNSELING

• NEGATIVE Test in High Risk Patient should be
  informed about false Negative Results related to
  the latest period.

23
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.

24
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.

25
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.

26
FACTORS ASSOCIATED WITH INCREASE
RISK OF PERINATAL TRANSMISSION.

• Low CD4 count.
• Scalp electrode scalp sampling.
• Prolonged rupture of membrane.
• Viral blood

27
FOLLOW UP

• CD4 Count (Monthly)
• Viral blood were viral RNA Quantitative
• measures are available.

28
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.

29
DELIVERY

• No evidence to support C/S to reduce
• the risk of infection.
• A R M , scalp electrode, fetal scalp
• sampling should be avoided.

30
POSTPARTUM

• AVOID BREAST FEEDING
• Risk ? by 10-20

31
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

32

• NO HIGH RISK
• ? Exposure to liquids and secretion that are
• potentially infection.
• ? OFFER AZT

33

• MUCOSAL EXPOSURE
• Blood Offer
• Fluid contaminated not offer
• SKIN EXPOSURE
• Blood offer
• Other fluid - not offer

34

• 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 ___________.

35
WHEN THE HIV TEST IS POSITIVE

• Check the following
• General Health Status - General well
  being
• - Constitutional symptoms
• - Nutritional assessment
• Past Medical History -
  Gynecologic/obstetrical history
  menstrual irregularity, previous
• abnormal Pap smears
• - Receipt of blood
  transfusions or
• 
  other blood products

36

• Drug History - Medication prescription and
• non-prescription
• - Complementary therapies
• - Recreational use smoking,
• alcohol, injection drug use
  including steroids, and street drugs

37

• SEXUAL HISTORY - STDs
• - Sexual activities
• - Previous sexual partners
• - Current sexual partners
• - Current sexual practices
• - Partners at risk
• - Method of contraception

38

• 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

39

• Psychosocial History
• Education
• Social supports
• Financial and employment
• background

40
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

41

• Respiratory
• Upper nasal and sinus congestion and pain
• Lower cough, sputum, shortness of breath,
• chest pain.
• Gastrointestinal
• - Taste - Dysphagia
• - Nausea - Vomiting
• - Vomiting - Abdominal rectal pain
• - Diarrhea - Jaundice
• - Hepatitis

42

• Genitourinary
• Dysuria
• Discharges
• Pelvic pain
• Neurologic System
• Central cognitive, memory, personality,
  seizures,
• weakness/pain/tingling/balanc
  e, visual
• changes
• Peripheral weakness/pain/tingling in
  extremities

43

• Psychiatric
• Mood
• Libido
• Cognitive
• Concentration
• Thought content
• Sleep

44
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

45
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

46
Cont. Baseline Physical Examination

• Chest and Cardiovascular - Air entry
• - Adventitial sounds
• - Murmurs
• - Tachycardia
• Abdominal and Rectal - Hepatosplenomegaly
• - Abdominal tenderness
• - Rectal lesions

47
Cont. Baseline Physical Examination

• Genito-urinary - Discharge
• - Genital lesions
• Pelvic - Vaginal discharge
• - Cervical lesions
• - Pelvic and adnexal
• mass and tenderness

48
Cont. Baseline Physical Examination

• Neurologic - Fundoscopic and visual field
  changes
• - Focal motor/sensory signs
• Mental Status - Mood/affect
• - Cognitive/perceptive
• - Memory/judgment/insight
• Skin - Rashes
• - Ulcers
• - Lesions, including Kaposis
  sarcoma (KS)

49
TRANSMISSION OF THE VIRUS

• Sexual intercourse
• anal and vaginal
• Contaminated needles
• Intravenous drug users
• needlestick injuries
• injections

50

• Mother ? child
• in utero
• at birth
• breast milk
• Organ/tissue donation
• Semen
• Kidneys
• Skin, bone marrow, corneas, heart valves,
  tendons, etc.

51
HIV Transmission Global Summary

• Type of exposure of Global Total
• Blood Transfusion 3 5
• Perinatal 5 10
• Sexual intercourse 70 80
• (Vaginal) (60 70)
• ( Anal) ( 5 10)
• Injecting drug use (sharing needles, etc) 5 10
  
• Health care (needlestick injury, etc) lt0-01

52
Cumulative AIDS cases reported to the
World Health Organization, June 1996

• The Americas - 690,042
• Europe - 167,578
• Africa - 499,037
• Oceania - 7,285
• Asia - ___29,707___
• T O T A L - 1,393,649

53

• 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

54

• 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 six-monthly if the
  presence of HPV is detected.

55

• For women with CD4 counts under 200 cells/mm3
• Three-monthly Pap smear
• Colposcopic examination using acetic acid
  visualization, to be repeated six-monthly

56
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

57
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.

58
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.

59
RISKS TO HEALTH WORKER

• Needle stick. Risk is .32 or 321000
• Mucous membranes Percutaneous exposure
• to infected blood. 0.03 or 31000
• No evidence that the virus is spread by
• mosquitoes, lice, bed bugs, swimming pools,
  
• sharing cups or eating and cooking utensils,
  
• toilets.

60
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

61
RISK OF BLOOD TRANSFUSION

• HEPATITIS - 1 100,000
• H I V - 1 500,000

62
HIV IN GYNECOLOGICAL PATIENT

• STD
• Recurrent candida infection refractory to
• conventional treatment.
• Recurrent cervical dysplasia - cervical ca.
• Recommend follow up in HIV positive.

63
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.

64
Changing HIV Therapy During Pregnancy

• Poor CD4 response
• Drugs with potential teratogenicity
• Poor viral load response
• Poor adherence to regimen
• Evidence of viral resistance

65
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

66
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 4872 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 IV ZDV and six week ZDV for the
  newborn.

67
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 (lt14 weeks).
• If therapy is stopped, stop and restart all ARV
  simultaneously
• Resistance testing for suboptimal viral
  suppression or failure.

68
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 HIV-infected pregnant women,
  regardless of antenatal viral load
• Consider delaying therapy until completion of
  first trimester.
• Offer scheduled cesarean delivery for women with
  viral loads gt1000 (based on most recent VL
  results).

69
WHEN SHOULD AN ADULT BE TREATED?

• Clinical Category CD4 count HIV RNA
  Recommendations
• Symptomatic Any value
  Treat
• --------------------------------------------------
  -------------------------------------------------
• Asymptomatic CD4 T cells lt200/mm3
  Treat
• HIV RNA any value
• -----------------------------------------
  -------------------------------
• CD4 T cells gt200/mm3 but Offer
  treatment if pt lt350/mm3,
  HIV RNA any value willing to accept
• --------------------------------------------------
  ------------------------------------------------
• Asymptomatic CD4 T cells gt350/mm3, HIV
  Some experts would
• RNA gt30,000 (bDNA) or treat
• gt55,000 (RT-PCR)
• ------------------------------------------
  -----------------------------
• CD4 T cells gt350/mm3, HIV Many
  experts would
• RNA lt30,000 (bDNA) or lt55,000 delay
  therapy
• (RT-PCR) observe

70
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

71
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

72
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.

73
Maternal Viral Load and Risk of Transmission
(Women Infants Transmission Study (WITS) )

• HIV 1 RNA Transmission N
• lt1000 0 0/57
• 1000 10,000 16.6 32/193
• 10,001 50,000 21.3 39/183
• 50,001 - 100,000 30.9 17/54
• gt100,000 40.6 26/64

74
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

75
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

76
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

77
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

78
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.

79
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.

80
PEOPLE NEWLY INFECTED WITH HIV IN 2001

• TOTAL 5 MILLION
• ADULTS 4.2 MILLION
• WOMEN 2 MILLION
• CHILDREN lt15 YEARS 800,000

81
NUMBER OF PEOPLE LIVING WITH HIV/AIDSAs of
End of 2001

• TOTAL 40 MILLION
• ADULTS 37.1 MILLION
• WOMEN 18.5 MILLION
• CHILDREN lt15 YEARS 3 MILLION

82
AIDS DEATH IN 2001

• TOTAL 3 MILLION
• ADULTS 2.4 MILLION
• WOMEN 1.1 MILLION
• CHILDREN lt15 YEARS 580,000

83

• TOTAL NUMBER OF CHILDREN ORPHANED BY AIDS, AND
  LIVING, END 2001
• 14 MILLION

84
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

85

• RECURRENT CANDIDA
• Oral Ketoconazole 400mg or
• Fluconazole 100mg
• ANTI TB
• INH or
• Rifamycin

86

• IMMUNIZATION
• Susceptible patients should received
• Hepatitis B
• Pneumococcal
• Influenza vaccine