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OBJECTIVES

EPIDIMIOLOGY Concentrate on Obstetrics and Gynecology The virus

CLINICAL FEATURES SCREENING + DIAGNOSTIC TESTS HIV in Obstetrics Population To screen or Not to screen.

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Cont. OBJECTIVES

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

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Cont. OBJECTIVES

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

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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

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NUMBER OF DEATHS 1999

TOTAL : 2.6 MILLION

MALES : 1 MILLIONFEMALES : 1.1 MILLIONCHILDREN : 470 HUNDRED THOUSAND

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NUMBER OF AIDS 1999

TOTAL : 33.6 MILLION

MALES : 17.6 MILLIONFEMALES : 14.8 MILLIONCHILDREN : 1.2 MILLION

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NUMBER OF AIDS 2000

TOTAL : 34.7 MILLION

MALES : 18.3 MILLIONFEMALES : 16.4 MILLION

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NUMBER OF DEATHS UNTIL 1999

TOTAL : 16.3 MILLION

MALES : 6.5 MILLIONFEMALES : 6.2 MILLIONCHILDREN : 3.6 MILLION

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ETIOLOGY

R N A : RETROVUSTYPE I : COMMENTISTTYPE II : MORE COMMON IN

WEST AFRICA

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1981 - Internal case1983 - Virus disease1984 - Antibodies tests developed

(Cumulative cases)

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PATHOLOGY

TARGET CELLS

CD4 Helper lymphocytes (Primary Target)

Macrophages

C N S

Placenta

SUPRESS IMMUNITY

INCREASE SUSCEPTIBILITY TO OPPORTUNISTIC

INFECTIONS AND NEOPLASMS

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I am an Obstetrician not an Internist, why should I be

HIV oriented?

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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 16:100090% 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.

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CLINICAL FEATURES

At the time of exposure asymptomatic

acute mild syndrome similar to mononucleosis

Latest Period (Window Phase) (Seroconvertion)

Viral isolation - Antigen (PCR)

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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

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CLASSIFICATION OF THE DISEASE

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SEROCONVERTION ILLNESS

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SCREENING TEST

To detect antibodies to the virus rather that the virus itself

ELISA – 3 weeks-3 months to appear

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CONFIRMATORY TEST

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

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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.

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PRE-TEST COUNSELING

Risks of transmission (including Mode)Risks of perinatal transmissionPotential 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.

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POST-TEST COUNSELING

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

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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.

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Testing for the partner. Psychological and emotional support Discuss the strategies available to maintain

better quality of life. Emphasis the importance of follow up.

Cont. PATIENT WITH POSITIVE TEST

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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.

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FACTORS ASSOCIATED WITH INCREASE

RISK OF PERINATAL TRANSMISSION.

Low CD4 count.

Scalp electrode – scalp sampling. Prolonged rupture of membrane. Viral blood

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FOLLOW UP

CD4 Count (Monthly)

Viral blood were viral RNA Quantitative measures are available.

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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.

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DELIVERY

No evidence to support C/S to reduce

the risk of infection. A R M , scalp electrode, fetal scalp

sampling should be avoided.

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POSTPARTUM

• AVOID BREAST FEEDING

Risk by 10-20 %

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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

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NO HIGH RISK Exposure to liquids and secretion that are potentially infection.

OFFER AZT

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MUCOSAL EXPOSURE

Blood Offer Fluid contaminated – not offer

SKIN EXPOSURE Blood offer Other fluid - not offer

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PRECAUTIONS:Double glovingEye coverage at deliveryAvoid mouth suction in resuscitating the neonatesCareful handling of needles + sharpsUse closed vacuum collection system for blood with

___________.

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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

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

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

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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

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Psychosocial History Education Social supports Financial and employment

background

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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

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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

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Genitourinary Dysuria Discharges Pelvic pain

Neurologic System Central: cognitive, memory, personality, seizures,

weakness/pain/tingling/balance, visual

changes Peripheral: weakness/pain/tingling in extremities

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Psychiatric Mood Libido Cognitive Concentration Thought content Sleep

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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

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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

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Cont. Baseline Physical Examination

Chest and Cardiovascular - Air entry- Adventitial sounds- Murmurs- Tachycardia

Abdominal and Rectal - Hepatosplenomegaly - Abdominal tenderness- Rectal lesions

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Cont. Baseline Physical Examination

Genito-urinary - Discharge- Genital lesions

Pelvic - Vaginal discharge- Cervical lesions- Pelvic and adnexal mass and tenderness

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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 Kaposi’s sarcoma (KS)

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TRANSMISSION OF THE VIRUS

Sexual intercourse anal and vaginal

Contaminated needles Intravenous drug users needlestick injuries injections

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Mother child in utero at birth breast milk

Organ/tissue donation Semen Kidneys Skin, bone marrow, corneas, heart valves,

tendons, etc.

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HIV Transmission: Global Summary

Type of exposure % of Global Total a) Blood Transfusion 3 – 5 b) Perinatal 5 – 10c) 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) <0-01

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

The Americas - 690,042Europe - 167,578Africa - 499,037Oceania - 7,285Asia - ___29,707___

T O T A L - 1,393,649

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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

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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.

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For women with CD4 counts under 200 cells/mm3:

Three-monthly Pap smear Colposcopic examination using acetic acid

visualization, to be repeated six-monthly

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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

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ZIDOVUDINE THERAPY

ANTEPARTUMOral 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.

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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.

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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.

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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

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RISK OF BLOOD TRANSFUSION

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

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HIV IN GYNECOLOGICAL PATIENT

STD Recurrent candida infection refractory to

conventional treatment. Recurrent cervical dysplasia - cervical ca.

Recommend follow up in HIV positive.

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Maternal Viral Load (VL), ZDV Treatment and the Risk of Perinatal HIV Transmission

Correlation between high maternal VL and transmissionTransmission observed at every VL level, including undetectable levelsNo HIV RNA threshold below which there was no risk of transmission.ZDV decreases transmission regardless of HIV RNA levelRecommendation: Initiate maternal ZDV regardless of plasma HIV RNA or CD4 counts.

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Changing HIV Therapy During Pregnancy

Poor CD4 response

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

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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

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CLINICAL SCENARIO 3Women 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 IV ZDV

and six week ZDV for the newborn.

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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 1Women 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 >1000 (based on most recent VL results).

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WHEN SHOULD AN ADULT BE TREATED?Clinical Category CD4+ count & HIV RNA RecommendationsSymptomatic 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 & (RT-PCR) observe

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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

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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

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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 identifiedNo differences in Bayley developmental scores in uninfected infants.

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

HIV – 1 RNA Transmission % N

<1000 0 0/571000 – 10,000 16.6 32/19310,001 – 50,000 21.3 39/18350,001 - 100,000 30.9 17/54>100,000 40.6 26/64

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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

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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

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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

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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%

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Scope of the Epidemic Among Women and Children

AIDS in women has risen from 7% early in the epidemic to 24% of adult cases today263 new AIDS cases reported in children in 199910,000 – 20,000 estimated children living with HIV infection300 – 400 babies continue to be born with HIV infection each year in the U.S.

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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.

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PEOPLE NEWLY INFECTED WITH HIV IN 2001

TOTAL 5 MILLION

ADULTS 4.2 MILLION WOMEN 2 MILLIONCHILDREN <15 YEARS 800,000

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

TOTAL 40 MILLION

ADULTS 37.1 MILLION WOMEN 18.5 MILLIONCHILDREN <15 YEARS 3 MILLION

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AIDS DEATH IN 2001

TOTAL 3 MILLION

ADULTS 2.4 MILLIONWOMEN 1.1 MILLIONCHILDREN <15 YEARS 580,000

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

14 MILLION

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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

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RECURRENT CANDIDA Oral Ketoconazole 400mg or Fluconazole 100mg

ANTI TB INH or Rifamycin

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IMMUNIZATION

Susceptible patients should received: Hepatitis B Pneumococcal Influenza vaccine