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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 co-
receptors 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 Worldwide predominant
 HIV-2 concentrated in Africa

Most
common

 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 prevalence-
0.3%
Estimated number of adults and
children newly infected with HIV
in 2007
HIV AND INDIA – AN OVERVIEW
 Highest HIV prevalence
in Maharashtra, Andhra
Pardesh and Karnataka
in the south; and
Manipur, Mizoram and
Nagaland in the north-
east.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 2 3 4 5 6 / 2 4 6 8 10
1° infection weeks years
Time following infection
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 recent / established advanced


DNA PCR
RNA PCR
p24 Ag
3rd gen ELISA
1st gen ELISA
Detuned ELISA
1wk 2wk 3wk 2mo 6mo 1yr 2yr 3yr
+8yr
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
 -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 Evidence of possible increased risk
retardation
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 insemin-
ation method
that introdu-
ces the semen
into her vagi-
na without
intercourse

HIV +VE HIV -VE


Planning pregnancy

Rapid spinning
of male partner
semen in lab
allows separa-
tion 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 pregnancy-
related 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
 HIV medications given
1. For the mother’s own health-treated as soon
as possible including first trimester.
2. To prevent mother to child transmission-
delaying 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”:
1. NRTIs (nucleoside or nucleotide reverse transcriptase inhibitors)
2. NNRTIs (non-nucleoside reverse transcriptase inhibitors)
3. PIs (protease inhibitors)
4. Fusion inhibitors
5. Integrase inhibitors Experimental stage

6. Chemokine Coreceptor Antagonists


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. Prevent Feto-maternal transmission.
2. Preserve and restore patient’s immune system.
3. Maintain a viral load as low as possible—
usually meaning keeping it undetectable.
4. Minimize side effects and drug interactions,
and avoid any permanent damage.
5. Prolong life and maintain quality of life.
6. Drug combination should be rational and permit
further sequencing if required.
Nucleoside/nucleotide reverse
transcriptase inhibitors (NRTI)
 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 .
 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
 Viral load (HIV-RNA  STDs and other
level) coinfections
 Genital tract viral load  Preterm delivery
 CD4 cell count  Placental disruption
 Clinical stage of HIV  Invasive fetal monitoring
 Unprotected sex with  Duration of membrane
multiple partners rupture (>2%)
 Smoking cigarettes  Substance abuse
 Vitamin A deficiency  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


 Birthto 14 days
 At 1-2 months of age
 At 3-6 months of age
 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 sulphameth-
oxazole 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
 No BCG should be given????????
Breast feeding
 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
 There is always risk to transmission of infection to
health care providers.
 RISK FACTORS
1. Deep injury
2. Visible blood on the device that caused the injury
3. A procedure that involved a large gauge hollow bore
needle directly placed in a vein or artery
4. Exposure to patients with AIDS or a high plasma viral
burden
5. 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.

 HAND PROTECTION Double gloves

 SKIN PROTECTION plastic sheet gown

 FACE PROTECTION mask, protective eye shields

 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

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