Download HIV INFECTION

HIV INFECTION
 The
estimated number of perinatally
acquired AIDS cases had decreased
dramatically over the last two decades. This
is predominantly due to the implementation
of prenatal HIV testing with antiviral therapy
given to the pregnant woman and then to her
neonate .
 In addition, highlyactive antiretroviral
therapy(HAART) has led to an increasing
number of people living with chronic HIV
infectio
RNA retroviruses : , HIV-1 and HIV-2.
 Transmission: sexual intercourse, blood or
blood-contaminated products, and mothers
may infect their fetuses
 The common denominator of clinical illness :
profound immunosuppression that gives rise
to a variety of opportunistic infections and
neoplasms.
 Sexual transmission occurs when mucosal
dendritic cells bind to the HIV envelope
glycoprotein gp120
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 two
chemokine receptors—CCR5 and CXCR4
 The CCR5 co-receptor is found on the cell
surface of CD4 positive (CD4+) cells in high
progesterone states such as pregnancy,
possibly aiding viral entry
 pregnancy has minimal effects on CD4+ Tcell counts and HIV RNA levels,
(the latter are often higher 6 months
postpartum than during pregnancy).
The incubation period from exposure to clinical
disease is days to weeks. Acute HIV infection is
similar to many other viral syndromes and
usually lasts less than 10 days.
 Common symptoms include fever,N/V, and night
sweats, ….
 After symptoms abate, the set-point of chronic
viremia is established. The progression from
asymptomatic viremia to AIDS has a median time
of approximately 10 years .
 Route of infection, the pathogenicity of the
infecting viral strain, the initial viral inoculum,
and the immunological status of the host all
affect the rapidity of progression
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The CDCP, ACOG, AAP,…recommend prenatal screening
using an opt-out approach.
In areas in which the incidence of HIV or AIDS is 1 per 1000
person years or greater or in women at high risk for
acquiring HIV during pregnancy, repeat testing in the
3rdtrimester
(HIGH RISK……..)
Screening is performed using an ELISA test with a
sensitivity of >99.5%.
A positive test is confirmed with either a Western blot or
(IFA) (high specificity).
Antibody can be detected in most patients within 1 month
of infection, and thus, antibody serotesting may not
exclude early infection.
For acute primary HIV infection, identification of viral
p24 core antigen or viral RNA or DNA is possible. Falsepositive confirmatory results are rare
If the rapid HIV test result in labor‘ and delivery is
positive :
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1. Tell the woman she may have HIV infection and that her
neonate also may be exposed
2. Explain that the rapid test result is preliminary and that falsepositive results are possible
3. Assure the woman that a second test is being performed to
confirm the positive rapid test result
4. To reduce the risk of transmission to the infant, immediate
initiation of antiretroviral prophylaxis should be recommended
without waiting for the results of the confirmatory test
5. After birth, discontinue maternal antiretroviral therapy
pending receipt of confirmatory test results
6. Teil the women that she should postpone breast feeding until
the confirmatory result is available because she should not breast
feed if she is infected with HIV
7. Inform pediatric care providers ,maternal test results ,so that
they may institute the appropriate neonatal prophylaxis
 mother-to-child
transmission is the most
common cause of pediatric HIV infections.
15 and 40% of neonates born to non-breastfeeding, untreated, HIV-infected mothers
are infected.
 Vertical transmission is more common with
preterm births, especially with prolonged
membrane rupture (>4 hr ROM)15% TO 25%
 women with maternal HSV-2 antibody had a
significant 50% increased risk of intrapartum
HIV-1 maternal-to-child transmission.
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MATERNAL FACTORS:
-AIDS (progressive diseas)
-low CD4
-High viral load
–Primary HIV
–Other STD
–NVD
–Age
–Malnutrition( Vit A)
–Smoking
–Drug abuse
FETAL FACTORS:
- Chorioamnionitis
–LBW
–Prematurity
–PROM>4hr
–Breast feeding
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Perinatal HIV transmission is most accurately correlated
with maternal plasma HIV RNA burden
1% with <400 copies/mL, and it was > 30 % with >100,000
copies/mL .
(ZDV) therapy that reduced these levels to <500
copies/mL also minimized the risk of transmission
although ZDV is effective in reducing transmission across
all HIV RNA levels.
Maternal infusions of HIV-1 hyperimmune globulin did
not alter the risk of transmission.
Transmission, however, has been observed at all HIV RNA
levels, including those that were nondetectable by
current assays. ( discordance between the viral load in
plasma and in the genital secretions).
The viral load should not be used to determine whether
to initiate antiretroviral therapy in pregnancy.
 Although
maternal morbidity and mortality
rates are not increased in seropositive
asymptomatic women, it appears that
adverse fetal outcomes may be increased .
 If the CD4+ T-cell count is <200/mm3,
primary prophylaxis for P. jiroveci (formerly
P. carinii) pneumonia is recommended with
sulfamethoxazole-trimethoprim or dapsone.
Pneumonitis is treated with oral or
intravenous sulfamethoxazole-trimethoprim
or dapsone-trimethoprim.
Even with treatment, the incidence of perinatal
complications in HIV-infected women is increased.
 Adverse fetal outcomes were associated with a CD4+
cell proportion of <15 percent.
- preterm birth was 20 %
-fetal-growth restriction was 24 %.
(adverse outcomes were even more prevalent in
developing countries.)
 Prenatal exposure to HAART may increase the risk for
neonatal neutropenia, although no long-term
hematological or hepatic toxicities have been
identified
 women given combination PI regimens had an
increased risk of very-lBW infants. Despite this,
combined therapy should not be withheld
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Effective contraception if pregnancy is
undesired.
 Certain antiviral medications decrease the
efficacy of hormonal contraception.
 Education for decreasing high-risk sexual
behaviors to prevent transmission and to
decrease the acquisition of other STD .
 High teratogenic potential are avoided if the
woman becomes pregnant.( efavirenz )
 Decrease HIV RNA viral load effectively
prior to pregnancy.
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· Standard prenatal laboratory surveys : (Cr,CBC, and
bacteriuria screening )
·Plasma HIV RNA quantification-"viralload" and CD4+
T-lymphocyte count as well as antiretroviral
resistance testing
· Serum hepatic transaminase levels
· HSV-1 and -2,CMV, toxo, and hepatitis C screening
.Baseline chest radiograph
· Tuberculosis skin testing (PPD)
· Evaluation of need for pneumococcal, hepatitis B,
and influenza vaccine ·
.Sonographic evaluation to establish gestational age.
 Treatment
is recommended for all HIVinfected pregnant women.
 Treatment reduces the risk of perinatal
transmission regardless of CD4+ T-cell count
or HIV RNA level.
 starting HAART regimen is two nucleoside
reverse transcriptase inhibitors (NRTIs) plus a
(NNRTI) or protease inhibitor(s).
 Because of an increased risk of
hepatotoxicity, nevirapine is reserved for
women with a CD4+ cell count <250
cells/mm3.
Recommendations
for Antiviral
Drug Use During
Pregnancy
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Continue current medication if viral
suppression adequate and patient tolerating
 - Avoid efavirenz in the first trimester .
 If virus detectable, order HIV antiretroviral
drug-resistance testing . If first trimester,
continue medications. If stopped, stop all
medications and then reinitiate in the second
trimester.
 .If not receiving zidovudine (ZDV)
antepartum, start IV ZDV in labor
 .Order
HIV antiretroviral drug-resistance
testing .
 Initiate HAART:
- Avoid efavirenz in the first trimester
- Use ZDV-containing regimen if feasible
- Avoid nevirapine in women with a CD4+
count>250 cells/mm3 .
 HAART should be initiated as early as
possible for maternal indications .
 If not receiving zidovudine antepartum, start
IV ZDV
Order HIV antiretroviral drug-resistance testing
.Initiate HAART:
- Consider delaying therapy until the start of the
second trimester (14weeks)
- Use ZDV-containing regimen if feasible
- Avoid nevirapine in women with a CD4+ count
>250 cells/mm3 .
ZDV monotherapy is controversial:
 - If used, use in women with HIV RNA levels
<1000 copies/mL
 - If not receiving zidovudine antepartum, start IV
ZDVin
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Order HIV antiretroviral drug-resistance
testing .
 initiate HAART with regimen based on prior
therapy history and resistance testing .
 Avoid efavirenz in the first trimester .
 Use ZDV-containing regimen if feasible .
 Avoid nevi rapine in women with a CD4+
count>250 cells/mm3 .
 If not receiving zidovudine antepartum, start
IV ZDV
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Order initial HIV laboratory assessment .
 Start zidovudine intravenous protocol .
 or . Start intravenous zidovudine plus a
single dose of nevirapine (NVP).
 if NVP initiated, consider adding lamivudine
for 7 days postpartum to decrease NVP
resistance .
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CD4+ count, HIV RNA viral load ,CBC ,LFT: 4 weeks
after beginning or changing therapy to assess
responseand evidence of toxicity.
HIV RNA viral load and CD4+ quantification are
determined each trimester.
If the HIV RNA viral load increases or does not
decrease appropriately, then medication compliance
and antiretroviral drug resistance are assessed.
Poor adherence to therapy appears to be a
significant problem in pregnancy.
Abnormal GCT and PI use ?
careful surveillance for :
interactions between antiretroviral drugs with TX for
opportunistic infection, methadone, and TB.
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Maternal HAART + intrapartum ZDV prophylaxis has
dramatically reduced the perinatal HIV transmission risk
from about 25 % to 2 % or less.
Optimal management of labor is uncertain,
If labor is progressing with intact membranes, artificial
rupture and invasive fetal monitoring are avoided.
Labor augmentation is used when needed to shorten the
interval-to-delivery to further decrease the risk of
transmission.
Operative delivery with forceps or vacuum extractor is
avoided if possible.
Postpartum hemorrhage is managed with oxytocin and
prostaglandin analogs because methergine and other ergot
alkaloids interact with reverse transcriptase and protease
inhibitors to cause severe vasoconstriction.
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Cesarean delivery has been recommended to decrease
HIV prenatal transmission.
(8533 mother-neonate pairs) Vertical HIV transmission was
reduced by approximately half when C/S was compared
with NVD. And when antiretroviral therapy was given in the
prenatal, intrapartum, and neonatal periods along with
C/S, the likelihood of neonatal transmission was reduced
by 87 % compared with other modes of delivery and
without antiretroviral therapy.
ACOG concluded that scheduled C/S should be discussed
and recommended for HIV-infected women whose HIV-1
RNA load exceeds 1000 copies/mL.(38 weeks ) .
Although data are insufficient to estimate such benefits of
cesarean delivery for women whose HIV RNA levels are
below 1000 copies/mL, it is unlikely that scheduled
cesarean delivery would confer additional risk reduction
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Antepartum : 100 mg orally five times daily, initiated at 14 to
34 weeks and continued throughout pregnancy.
 Intrapartum: During labor, IV zidovudine in a 1-hour initial dose
of 2 mgjkg, followed by a continuous infusion of 1 mgjkgjhr until
delivery.
 Neonate: Begin at 8 to 12 hours after birth, and give syrup at
2 mgjkg Q6h for 6 weeks.
 IV dosage for infants who cannot tolerate oral intake is 1.5 mgjkg
IV Q6h).
( alternative regimens include 200 mg TID or 300 mg BID)
 beFor elective C/S, IV zidovudine is begun at least 3 hr prior to
surgery.
 For PROM or labor with a planned operative delivery, the loading
dose may be given over the half hour prior to surgery.
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the first DNA PCR test for HIV : within 48 hours of birth.
Testing of the umbilical cord blood should not be done
due to possible risk of contamination with maternal
blood.
A positive test will provisionally mean that the newborn
infant is infected and further HIV DNA/RNA testing should
be undertaken straight away to confirm the diagnosis and
enable an early switch from ZDVm to ART.
If negative, further HIV DNA tests at 6 &12 weeks from
birth
The third test may be more important if the risk of
transmission is considered to be high and ART prophylaxis
is prescribed for four weeks. Further investigation of any
positive result should be undertaken without delay to
allow appropriate early therapy if HIV infection is
confirmed.
Where HIV DNA testing is not available, HIV RNA
assays can be used but the pitfalls of both low
copy number RNA false positives and negative
results during or shortly after infant ART for
PMTCT need to be recognized and such results
interpreted with caution.
 Even for HIV-exposed children testing negative,
follow up and documentation of seroreversion by
an HIV antibody test is recommended at 15–18
months.
 low titres of maternal antibody can be
detected even at 15 months in uninfected
children and should be interpreted with
caution or the test delayed until 18 month
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 Vertical
transmission is increased by breast
feeding, and it generally is not recommended
in HIV-positive women.
 The probability of HIV transmission per liter
of breast milk ingested is estimated to be
similar in magnitude to heterosexual
transmission with unsafe sex in adults