Hiv In Pregnancy Final

Dr Nidhi Pathak DNB Trainee Obs & Gynaec Kasturba Hospital BHEL Coordinator: Dr Pomila Sachdeva

HIV

CD4 cell with attached HIV

HIV Life Cycle step 1 HIV binds to the CD4 receptor and CCR5 or CXCR4 coreceptors in order to fuse with the cell membrane.

HIV Life Cycle step 2 The HIV RNA is released into the cell, along with viral enzymes.

HIV Life Cycle Step 3 reverse transcriptase, builds a DNA copy of the original viral RNA. the DNA form, is integrated into the human cell's DNA "provirus" This step is helped by enzyme integrase

HIV Life Cycle step 4 An active virus is transcribed into RNA by human cell enzymesand forms new parts of the virus.

HIV Life Cycle step 5 new virions (complete viruses) are assembled together in an infected cell and bud off to infect a new cell

Types of HIV viruses 

Two types of HIV  

HIV-1 HIV-2

Worldwide predominant concentrated in Africa Most common

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Greater than 90% of HIV-1 infection belong to group-M which has 9 subtypes. Subtype C is predominant in India.

HIV AND INDIA – AN OVERVIEW India population 1 billion  Half are adults.  Estimated people living with AIDS/HIV- 2.4 million.( much less than previously estimated 5 million).  Adult (15 years or above) HIV prevalence0.3% 

Estimated number of adults and children newly infected with HIV in 2007

HIV AND INDIA – AN OVERVIEW 

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Highest HIV prevalence in Maharashtra, Andhra Pardesh and Karnataka in the south; and Manipur, Mizoram and Nagaland in the northeast.1 Andhra Pradesh, Maharashtra, Tamil Nadu and Karnatakaaccount for around 63% of all people living with HIV in India

HIV AND INDIA – AN OVERVIEW Age group

HIV prevelance Male

Female

Total

15-19

0.01

0.07

0.04

20-24

0.19

0.17

0.18

25-29

0.43

0.28

0.35

30-34

0.64

0.45

0.54

35-39

0.53

0.23

0.37

40-44

0.41

0.19

0.30

45-49

0.48

0.17

0.33

Total Age (15-49)

0.36

0.12

0.28

HIV Sentinel Surveillance and HIV Estimation, 2006", NACO, 2007

Typical Type 4 Pattern of spread of infection vulnerable group s/a iv drug user/female sex worker

Bridge population s/a clients of sex worker and sex partner of IVDU

General population

Which patient has HIV

We can’t tell. That’s why we screen for HIV

Screening of HIV in Pregnancy

Doctor and caregivers

The newborn

Pregnant female

HIV Testing during Pregnancy 

Advantages:  Possible

treatment of mother  Reduce risk of mother-to-child transmission  Future family planning issues  Precautions against further spread  If negative, advise about HIV prevention

Counseling is important!

HIV testing during pregnancy Two main approaches:  Opt-in testing: Woman can not be given HIV test unless she requests to be tested  Opt-out testing: Health care providers must inform pregnant women that HIV test will be included in the standard group of tests pregnant women receive. She will receive the test unless she refuses.  CDC recommends-opt-out approach.

TYPICAL PRIMARY HIV-1 INFECTION symptoms

symptoms

HIV proviral DNA HIV antibodies ‘window’ period

HIV viral load

HIV-1 p24 antigen 0 1 1° infection

2

3 weeks

4

5

6

/

2

Time following infection

4

6

8

years

10

Screening and diagnostic test Counseling is a must.  ELISA  Western Blot  PCR DNA  PCR RNA  P-24 Antigen 

HIV TEST SPECTRUM gp160 gp120

p68 p55 p53 gp41 -45 p40 p34 p24 p18 p12

early DNA PCR RNA PCR p24 Ag 3rd gen ELISA 1st gen ELISA Detuned ELISA

1wk

recent / established

2wk 3wk +8yr

2mo 6mo

advanced

1yr 2yr

3yr

ELISA -rapid test  detects antibodies  if negative,no further testing,person is considered uninfected. 

SIMPLE ASSAYS: HIV DETERMINE        

Detect HIV-1 & HIV-2 Cannot differentiate between HIV types Procedural control using anti human IgG Can test using whole blood, serum or plasma Widely available No additional reagents required Storage at room temperature 15 minutes to get result

WESTERN BLOT  

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

-confirmatory test if both ELISA and western blot are positive-HIV infected. if negative-HIV negative. indeterminate western blot-test is positive for antibodies to some parts,but not to 2 of 3 key parts; requires further testing

P-24 antigen test-window period.  Viral Nucleic Acid Amplification(NAAT) tests.  Recently, a qualitative nucleic acid test: Aptima, approved by FDA for diagnosis of acute HIV and for blood donor screening.  Ora Quick Rapid HIV-1 test, results available in 20 mins. 

Generations of HIV antibody tests First generation-original ELISA test  Second generation-improved ELISA, detecting IgG antibody.  Third generation-detects both IgM and IgG antibody. (blood donation)  Fourth generation-combine both antibody and p-24 antigen detection. 

Pregnancy Effects on HIV No change in – Mortality – Progression to AIDS – HIV RNA  In all women, the absolute CD4 count decreases no matter whether HIV-positive or negative (pregnancy does not make HIV worse)  In HIV-positive women, percentage of CD4 cells should not change and viral load should not change because of pregnancy. 

Effect of HIV on pregnancy Pregnancy Outcome

Relationship to HIV Infection

Spontaneous abortion

Limited data, but evidence of possible increased risk

Stillbirth

No association noted in developed countries; evidence of increased risk in developing countries

Perinatal mortality

No association noted in developed countries, but data limited; evidence of increased risk in developing countries

Newborn mortality

Limited data in developed countries; evidence of increased risk in developing countries

Intra-uterine growth retardation

Evidence of possible increased risk

Effect of HIV on pregnancy Pregnancy Outcome

Relationship to HIV Infection

Low birth weight

Evidence of possible increased risk

Preterm delivery

Evidence of possible increased risk, especially w/ more advanced disease

Pre-eclampsia

No data

Gestational diabetes

No data

Amnionitis

Limited data; more recent studies do not suggest an increased risk; some earlier studies found increased histologic placental inflammation, particularly in those with preterm deliveries

Oligohydramnios

Minimal data

Fetal malformation

No evidence of increased risk

Clinical scenarios • Women diagnosed prior to pregnancy • Women diagnosed during pregnancy • Women diagnosed during labour

Women diagnosed prior to pregnancy Foremost important is starting of Anti HIV Medication  Counseling for alternatives to pregnancy such as adoption, risk involved, transmission to child, partner counseling and testing. 

Planning pregnancy An insemination method that introduces the semen into her vagina without intercourse HIV +VE

HIV -VE

Planning pregnancy Rapid spinning of male partner semen in lab allows separation of virus. HIV -VE

HIV +VE

Women diagnosed during pregnancy.

Antenatal care        

Most HIV-infected women will be asymptomatic Watch for signs/symptoms of AIDS and pregnancyrelated complications Unless complication develops, no need to increase number of visits Treat STDs and other coinfections Counsel against unprotected intercourse Avoid invasive procedures and external cephalic version Give antiretroviral agents, Counsel about nutrition

WHO SHOULD TAKE ANTI HIV MEDICATION ????

WHO SHOULD TAKE ANTI HIV MEDICATION ???? Anti HIV therapy should be offered to all HIV infected Pregnant women irrespective of CD4 Count & HIV RNA level

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HIV medications given 1. 2.

For the mother’s own health-treated as soon as possible including first trimester. To prevent mother to child transmissiondelaying medications until after first trimester can be considered.

if the women is already on anti–HIV medications  Pregnancy identified during first trimester-risks and benefits of continuing the regimen considered.  Pregnancy is identified after first trimester-current regimen to be continue AZT has to be part of the treatment regimen.

ANTI HIV MEDICATION The single most significant fact that separates HIV-positive women from HIV-positive men is that more than 60 percent of women take care of at least one child under the age of 16.# These women regularly have to put their children first, which means that they often can’t make doctor’s appointments or take their medications as prescribed.

# thebody.com : the complete HIV/ AIDS source

ANTI HIV MEDICATION HIV medications fall into four types or “classes”:

4.

NRTIs (nucleoside or nucleotide reverse transcriptase inhibitors) NNRTIs (non-nucleoside reverse transcriptase inhibitors) PIs (protease inhibitors) Fusion inhibitors

5.

Integrase inhibitors

6.

Chemokine Coreceptor Antagonists

1. 2. 3.

Experimental stage

All four classes of medications have been designed to interfere with HIV's ability to copy itself—that is, to reproduce inside your body.

HAART Combination of two or more classes of drug.  Prevents development of resistance  Helps in sequencing.  Dramatically reduces mortality and prolongs life.  START:-Short Term Anti Retroviral therapy 

Goals of Treatment 1. 2. 3. 4. 5. 6.

Prevent Feto-maternal transmission. Preserve and restore patient’s immune system. Maintain a viral load as low as possible— usually meaning keeping it undetectable. Minimize side effects and drug interactions, and avoid any permanent damage. Prolong life and maintain quality of life. Drug combination should be rational and permit further sequencing if required.

Nucleoside/nucleotide reverse transcriptase inhibitors (NRTI)  

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First class of drugs developed. Example:- abacavir, didanosine, emtricitabine, lamivudine,, tenofovir, and zidovudine. Analogues of nucleosides. Reverse transcriptase(RT) tries to use one of these false building blocks, it stops (terminates) the work of the RT enzyme.

DRUG

TOXICITY

REVERSE TRANSCRIPTASE INHIBITORS ZIDOVUDINE

Granulocytopenia,myopathy,lactic acidosis,hepatomegaly,headache nausea, Anemia

LAMIVUDINE

hepatotoxicity

STAVUDINE

Peripheral neuropathy,pancreatitis ,lactic acidosis,hepatomegaly ,neuromuscular weakness

Non-nucleoside reverse transcriptase inhibitors Target RT  Directly gum up the RT and stop it from working.  Example:- delavirdine,efavirenz,etravirine and nevirapine . 

Protease inhibitors  



Stop the action of the protease enzyme, which HIV needs to produce a fully mature virus. Example:- atazanavir, darunavir, fosamprenavir, Telzir, indinavir, lopinavir/ritonavir, nelfinavir, ritonavir, saquinavir, and tipranavir. Atazanavir and lopinavir/ritonavir are recommended as preferred agents in a protease inhibitor-based starting regimen.

Fusion inhibitors 

  

Enfuvirtide (Fuzeon, ENF, T-20) is the only approved drug in this class. It blocks fusion of HIV with the cell membrane. Given as a subcutaneous injection, Usually reserved for treatment in persons with virus that is resistant to other drugs.

Integrase inhibitors 





Raltegravir blocks the integrase enzyme and prevents HIV from being spliced into the human chromosome. Highly effective against HIV and have few side effects. May become first line agents as we gain experience in using them.

Chemokine Coreceptor Antagonists Maraviroc is the drug that blocks CCR5, which the virus uses as a co-receptor for cell entry.  Currently reserved for drug resistant HIV. 

Treatment regimen 

Zidovudine monotherapy: Low

viral load (<10,000 copies/ml)  Wild type virus  Not requiring HAART for maternal health  HIV diagnosed during labour and patient willing for LSCS.  Nevirapine is added 6 hours before planned LSCS to reduce MTCT.  Ziduvidine monotherapy reduces transmission from 25.5% to 8.3% in non breast feeding population.

Treatment regimen 

HAART  High

viral load (>10,000 copies/ml)  For maternal health.  More efficacious in preventing MTCT  Short term HAART (START) is considered to reduce MTCT and if women diagnosed late in pregnancy

Treatment regimen Nevirapine single dose regime to mother and one dose of NVP syrup to infant has become most widely implemented strategy & shown promising results in reducing MTCT, but long term studies are needed.  WHO recommends antenatal AZT+NVP in low resourced country. 

Delivery options for HIV positive pregnant women 

Cesarean delivery recommended when her viral load is unknown or is >1000 copies/ml at 36 weeks of pregnancy.  She has not taken any anti-HIV medications or has only taken AZT during her pregnancy  She has not received prenatal care until 36 weeks into her pregnancy or later . 

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To be most effective in preventing transmission, cesarean section should be scheduled at 38 weeks or should be done before the rupture of membranes.



Vaginal delivery recommended when she has been receiving prenatal care throughout her pregnancy  She has a viral load <1000 copies/ml at 36 weeks.  Maternal wishes should be considered. 

Women who present late in pregnancy:  Treatment with Nevirapine as it crosses placenta plus zidovudine i.v. and one another drug  Continue until after delivery at least until viral load is<50 copies/ml 

Women diagnosed in labour 

AZT should be started 3hours before a scheduled cesarean delivery and should be continued until delivery. IV AZT should be given throughout labor and delivery for vaginal delivery.

Mother-to-Child Transmission 25–35% of HIV positive pregnant mothers will pass HIV to their newborns in the absence of any HIV treatment.  In the absence of breastfeeding: 

 30%

of transmission in utero  70% of transmission during the delivery

Risk Factors for Mother-to-Child Transmission 

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Viral load (HIV-RNA level) Genital tract viral load CD4 cell count Clinical stage of HIV Unprotected sex with multiple partners Smoking cigarettes Vitamin A deficiency

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STDs and other coinfections Preterm delivery Placental disruption Invasive fetal monitoring Duration of membrane rupture (>2%) Substance abuse Breastfeeding

Other interventions • Avoid fetal scalp electrodes and other interventions if vaginal delivery occurs • wash baby thoroughly as soon as feasible to reduce contamination with maternal secretions • do not give injections (vitamin K) to the baby before washing • resuscitation should be as atraumatic as possible • avoid breast feeding which approximately doubles the risk of transmission without intervention

HIV positive women and their babies after birth 

Preliminary HIV test for babies  Birth

to 14 days  At 1-2 months of age  At 3-6 months of age

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It is recommended that all babies born to HIV positive mothers receive a 6wks course of oral AZT-begin within 6-12 hrs of birth. PCP prophylaxis –combination of sulphamethoxazole and trimethoprim. This treatment should be started when baby is 4-6 wks old and 6 wks course of AZT is complete. Complete blood picture should be done, Monitor for signs of anemia

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No BCG should be given????????

Breast feeding  

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Transmission rates - 30%-40% Advised against but WHO(2001) recommends continuing breast feeding with early weaning by 6 months in developing countries. Cumulative risk with breast feeding over time and no period is without risk Risk of HIV transmission through breast feeding is greatest when infants are fed solid food or even water or animal milk before 6 months of age.

Risk factors for transmission of infection Maternal HIV status(CD4count)  Maternal plasma/or milk RNA viral load  Duration of breast feeding  Breast health  Infant health 

Risk to care givers   1. 2. 3. 4. 5.

There is always risk to transmission of infection to health care providers. RISK FACTORS Deep injury Visible blood on the device that caused the injury A procedure that involved a large gauge hollow bore needle directly placed in a vein or artery Exposure to patients with AIDS or a high plasma viral burden Long surgical time

[panlilio et al-orthopaedic n gynecologist are at more risk ]

INCREASED RISK         

When patients blood loss > 250ml Procedure > 1hr burn associated with Trauma Skin contact,including garment soakage Use of fingers while suturing Holding tissue that was being sutured Lot of washing of open wounds and debridement 0.3% after percutaneous exposure to infected blood 0.09%after mucous membrane exposure

STEPS IN PREVENTING THE RISK OF TRANSMISSION OF HIV 

PREOPERATIVE SCREENING.

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HAND PROTECTION Double gloves

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SKIN PROTECTION plastic sheet gown



FACE PROTECTION mask, protective eye shields

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NO TOUCH TECHNIQUE



APPLY UNIVERSAL PRECAUTION

STEPS AFTER ACCIDENTAL EXPOSURE 

PROVIDE IMMEDIATE CARE TO THE SITE



DETERMINE THE RISK ASSOCIATED WITH EXPOSURE



EVALUATE EXPOSURE SOURCE

POST EXPOSURE PROPHYLAXIS BASIC REGIMEN  Zidovudine 600mg/day in 2-3 divided dose along with lamivudine 150mg twice daily OR  Lamivudine + Stavudine 40mg twice daily OR  Diadanosine400mg daily + Stavudine 40mg twice daily [ PEP-within 72 hrs after exposure and monitor for drug toxicity for at least 2 weeks]

POST EXPOSURE PROPHYLAXIS EXPANDED REGIMEN  Lopinavir/ritonavir[LPV/RTV][protease inhibitor] 400mg/100mg bid should be added to above regimen for 4 weeks