HIV IN PREGNANCY

Epidemiology
• Worldwide,in 2012 there were 35.3 million HIV infected persons ,2.3
million new cases of HIV infection; and 1.6 million HIV-related deaths.
• In 2010, women accounted for 20% of all HIV/AIDS.
• Comparing 2008 with 2011, HIV incidence decreased in women.
• Perinatally acquired AIDS cases has decreased during the past two
decades is due to the prenatal HIV testing and antiviral therapy.
• In addition, (HAART) has led to an increasing number of people living
with chronic HIV
Etiopathogenesis
• Causative agents of AIDS are RNA retroviruses termed human
immunodeficiency viruses, HIV-1 and HIV-2.
• Transmission- sexual intercourse(major mode),blood or blood-
contaminated products, and
• Male to female transmission is about double compared to female to
male transmission.
• Sexual transmission occurs when mucosal dendritic cells bind to the
HIV envelope glycoprotein(gp120). These dendritic cells then present
the viral to T lymphocytes. The CD4 site serves as receptor,
Coreceptors are necessary for viral entry into the cell, and two
chemokine receptors— CCR5 and CXCR4

• CCR5 coreceptor is found on the cell surface of CD4 positive (CD4+)

cells in high progesterone states such as pregnancy, possibly aiding
viral entry.
Clinical Manifestations

• The incubation period (3 to 6 weeks) Acute HIV infection (lasts

less than 10 days) set point of chronic viremia

• The progression from asymptomatic viremia to AIDS has a median

time of approximately 10 years.

• rapidity of progression- depends on route of infection, the

pathogenicity of the infecting viral strain, the initial viral inoculum,
and the immunological status of the host.
• Generalized lymphadenopathy, oral hairy leukoplakia, aphthous
ulcers, and thrombocytopenia indicate disease progression.
• Opportunistic infections associated with AIDS include esophageal or
pulmonary candidiasis; persistent herpes simplex or zoster lesions;
condyloma acuminata; pulmonary tuberculosis; cytomegaloviral
pneumonia, retinitis, or gastrointestinal disease; molluscum
contagiosum; Pneumocystis jiroveci pneumonia; toxoplasmosis; and
others.
• A CD4+ count < 200/mm3 is also considered definitive for the
diagnosis of AIDS.
• Effect of Pregnancy on HIV- Pregnancy has minimal effects on CD4+ T-
cell counts, HIV RNA levels or disease progression.

• Effect of HIV on Pregnancy- important implication for the fetus

because of the risk of vertical transmission.
• Incidence of abortion, prematurity,preeclampsia and IUGR are
inconclusive.
• Maternal morbidity and mortality are not increased by pregnancy.
Prenatal HIV Screening
• Opt-out approach- due to this HIV testing rates have increased.
• In areas where incidence of HIV is 1 per 1000 person-years or greater, or in
women at high risk, repeat testing in the third trimester is recommended.
• Screening- by EIA with a sensitivity > 99.5 percent. A positive test is
confirmed with either a Western blot or immunofuorescence assay (IFA),
both have 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.
“rapid” HIV test - should be done for undocumented HIV status at delivery
- can detect HIV antibody in 60 minutes or less
- sensitivities and specificities comparable with those of
conventional ELISAs

Negative rapid test A positive rapid test.

no need of should be confirmed

confirmation with a Western blot or IFA test
If the rapid HIV test result in labor and delivery is positive :
Strategy for Rapid (HIV) Testing of Pregnant Women in Labor
1. Tell the woman she may have HIV infection
2. false-positive results are possible
3. Assure the woman that a second test is being performed to confirm
4. immediate initiation of antiretroviral prophylaxis without waiting for confirmatory test
results.
5. Once the woman gives birth, discontinue maternal antiretroviral therapy till the confirmatory
test result
6. she should postpone breast feeding until the confirmatory resul
7. Inform pediatric care providers for neonatal prophylaxis
Maternal and Perinatal
Transmission
• Transplacental HIV transmission can occur early, however, mother-to-child
transmission at the time of delivery is the most common cause of pediatric HIV
infections.
• Between 15 - 40 % of neonates born to non–breast-feeding, untreated, HIV-
infected mothers are infected.
• 20 % of transmission occurs before 36 weeks gestation, 50 % in the days
before delivery, and 30 % intrapartum.
• Intrapartum transmission can occur during labour through maternal-fetal
exchange of blood.
• Transmission rates for breast feeding may be as high as 30 to 40 % and are
associated with systemic HIV viral burden
Risk factors associated with Perinatal HIV transmission-

Clinical factors. - advanced HIV disease in the mother

- failure to receive ART
Obstetric factors - Preterm delivery
- risk increases every hour after membrane ruptures
- chorioamnionitis
- Obstetric procedures- chorionic villus sampling,
amniocentesis, invasive intrapartum monitoring.
Maternal co-infection with another Sexually transmitted disease during pregnancy.
Women with maternal HSV-2 antibody have a significant 50% increased risk of intrapartum HIV-1 maternal-to-child transmission.
• Perinatal HIV transmission is correlated with maternal plasma HIV
RNA burden.
• Transmission of HIV infection, however, has been observed at all HIV
RNA levels, including those that were non- detectable.
• Therefore, the viral load should not be used to determine whether to
initiate antiretroviral therapy in pregnancy.
Preconceptional Counselling

• Effective contraception should be discussed if pregnancy is undesired

• Psychological support, if patient chooses to continue pregnancy.
• Education for decreasing high-risk sexual behaviors to prevent
transmission and to decrease the acquisition of other sexually
transmitted disease
Management During Pregnancy
The initial assessment of an HIV-infected pregnant woman includes:
• serum creatinine, hemogram, and bacteriuria screening
• Plasma HIV RNA quantification—“viral load,” CD4+ T-lymphocyte count, and antiretroviral resistance testing
• Serum hepatic aminotransferase levels

• HSV-1 and -2, cytomegalovirus, toxoplasmosis, and hepatitis C serology screening

• Baseline chest radiograph

• Tuberculosis skin testing—purified protein derivative (PPD) or INF-Y

• Evaluation of need for pneumococcal, hepatitis B, hepatitis

A, Tdap, and influenza vaccines
• Ultrasound scan for fetal anomalies after 1st trimester exposure to HAART.
Antiretroviral Therapy
• Treatment is recommended for all HIV-infected pregnant women irrespective of disease
status to reduce the risk of perinatal transmission.
• Treatment reduces the risk of perinatal transmission regardless of CD4+ T-cell count or
HIV RNA level.
• In general, HAART is begun if the woman is not already receiving one of the regimens.
• Regardless of what regimen is begun, adherence is important because the risk of viral
drug resistance is lessened.
• Women already taking HAART at pregnancy onset are encouraged to continue the
regimen if there is adequate viral suppression.
• Currently used antiretroviral medications are reviewed to avoid those with high
teratogenic potential. A specific example is efavirenz, which has significant teratogenic
effects on primate fetuses
 HIV-infected woman taking • Continue current medication
ART who becomes pregnant

 HIV-infected woman previously • HIV antiretroviral drug-resistance testing

Taking ART but not on medications • Initiate HAART with regimen based on prior
currently therapy history and resistance testing

 HIV-infected woman who • HAART should be initiated as early as possible

is antiretroviral naïve for maternal indications; if high CD4 count and
low HIV RNA level, can consider delaying
initiation of HAART until the second trimester

 HIV-infected woman on no • Start IV ZDV during labor—2 mg/kg IV load over

antiretroviral medication who 1 hour, then 1 mg/kg/hr until
presents in labor delivery
The 2010 revised PMTCT recommendations are based on two key approaches:
• Lifelong ART for HIV-infected women in need of treatment for their own health,
also safe and effective in reducing MTCT.
• ARV prophylaxis to prevent MTCT during pregnancy, delivery and breastfeeding
for HIV-infected women not in need of treatment.
Eligibility criteria for initiating antiretroviral treatment or prophylaxis in
HIV- infected pregnant women based on CD4 cell count and WHO clinical stage

CD4 cell count available

CD4 cell count
not available CD4 ≤350 CD4 >350
cells/mm3 cells/mm3
WHO clinical
ARV prophylaxis ART ARV prophylaxis
stage 1
WHO clinical
ARV prophylaxis ART ARV prophylaxis
stage 2
WHO clinical
ART ART ART
stage 3
Antiretroviral treatment options recommended for HIV-infected
pregnant women who are eligible for treatment

Maternal ART + infant ARV prophylaxis

Mother
Maternal antepartum daily ART, starting as soon as
possible irrespective of gestational age, and continued
during pregnancy, delivery and thereafter.
Recommended regimens include:
AZT + 3TC + NVP or
AZT + 3TC + EFV* or
TDF + 3TC (or FTC) + NVP or TDF + 3TC (or FTC) + EFV*
Infant
Daily NVP or twice-daily AZT from birth until 4 to 6 weeks
of age (irrespective of the mode of infant feeding).
ARV-prophylaxis options recommended for HIV-infected pregnant women who
do not need treatment for their own health
Maternal AZT + infant ARV
prophylaxis
(Option A)
Mother
 Antepartum twice-daily AZT starting
from as early as 14 weeks of
gestation and continued during
pregnancy.
 At onset of labour, sd-NVP and
initiation of twice daily AZT + 3TC
for 7 days postpartum.
(Note: If maternal AZT was provided for
more than 4 weeks antenatally,
omission of the sd-NVP and AZT + 3TC
tail can be considered; in this case,
continue maternal AZT during labour
and stop at delivery).
Maternal triple ARV prophylaxis
(Option B)
Mother
 Triple ARV prophylaxis starting from
as early as 14 weeks of gestation
and continued until delivery, or, if
breastfeeding, continued until 1
week after all infant exposure to
breast milk has ended.
Recommended regimens include:
AZT + 3TC + LPV/r or AZT + 3TC + ABC
or
AZT + 3TC + EFV or
TDF + 3TC (or FTC) + EFV
• The neural-tube defect risk associated with efavirenz is restricted to the first 6
weeks of pregnancy. Thus, efavirenz can be continued if the woman presents after
this time and if adequate virological suppression is documented.
• Avoid nevirapine in women with a CD4+ count > 250 cells/mm3
• Until recently, addition of zidovudine to all regimens was recommended.
Currently, however, in women with adequate viremia suppression with a regimen
not containing zidovudine, continuation of the current regimen is appropriate.
• Zidovudine is given intravenously during labor and delivery to women with an HIV
RNA viral load > 400 copies/mL or who have an unknown viral load near delivery
• A 2 mg/kg load is infused over 1 hour followed by zidovudine 1 mg/kg/hr until
delivery.
Laboratory Assessment

• CD4+ count, HIV RNA viral load, CBC, and LFT are done 4 weeks after
beginning the therapy to assess response and exclude toxicity.
Thereafter HIV viral load measured monthly until RNA levels are
undetectable.
• CD4 T-lymphocyte and HIV RNA levels can then be measured every
trimester.
• If the HIV RNA viral load increases or does not decrease appropriately,
then medication compliance and antiretroviral drug resistance are
assessed.
Complications of HIV Infection

• If the CD4+ T-cell count is < 200/mm3, primary prophylaxis for

Pneumocystis jiroveci pneumonia is recommended with
sulfamethoxazole- trimethoprim or dapsone.

• Other symptomatic opportunistic infections that may develop are

from toxoplasmosis, herpes virus, mycobacteria, and candida.

• Maternal HIV infection has also been associated with fetal-growth

restriction, preeclampsia, and preterm membrane rupture
Medication Toxicity
• Prenatal exposure to HAART may increase the risk for neonatal
neutropenia and anemia, although no long-term hematological or
hepatic toxicities documented

• long-term follow-up is recommended for all infants exposed in utero

to antiviral medications.
Prenatal HIV Transmission

• Maternal HAART treatment along with intrapartum zidovudine

prophylaxis has reduced the perinatal HIV transmission risk from
approximately 25 percent to 2 percent or less.
• artificial rupture of membrane and invasive fetal monitoring are avoided.
• Labor augmentation is used when needed but operative delivery with
forceps or vacuum extractor is avoided if possible.
• Postpartum hemorrhage is managed with oxytocin and prostaglandin
analogues.
• Methergine and other ergot alkaloids adversely interact with reverse
transcriptase and protease inhibitors to cause severe vasoconstriction.
• Cesarean delivery has been recommended to decrease HIV prenatal transmission.
• When antiretroviral therapy was given in the prenatal, intrapartum, and neonatal
periods along with cesarean delivery, the neonatal transmission was reduced by 87
% compared with vaginal delivery and without antiretroviral therapy.
• ACOG(2010b) concluded that scheduled cesarean delivery should be recommended
for HIV-infected women whose HIV-1 RNA load exceeds 1000 copies/mL.
• Scheduled delivery is recommended at 38 weeks gestation in these women.

• HIV-infected women undergoing a scheduled cesarean delivery should be given IV

zidovudine as a loading dose followed by 2 more hours of continuous maintenance
therapy—a total of 3 hours of infused zidovudine.
Breast Feeding

• The virus is secreted in breast milk and breast feeding is not recommended
for HIV-positive women in the United States.
• 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
• The risk is related to the maternal HIV RNA level, HIV disease status, breast
health, and duration of breast feeding
• WHO(2010) has recommended exclusive breast feeding the first 6 months of
life for infants of women living in developing countries in which infectious
diseases and malnutrition are the primary causes of infant deaths.
Postpartum Management

• Healthy women with normal CD4+ T-cell counts and low HIV RNA
levels may discontinue treatment after delivery and be closely
monitored according to adult guidelines.
• antiretroviral drugs may affect oral contraceptive hormone levels and
possibly of injectable agents
• hormonal contraception use is safe for these women and that
condom use should be encouraged regardless of contraceptive
method.
• Intrauterine devices may be an acceptable choice in some women
with normal immunocompetence and a low risk for STIs.
Thank You
• After initial infection, the level of viremia usually decreases to a set
point, and patients with the highest viral burden progress more
rapidly to AIDS and death