• Factors that influence maternal transmission
  • Stages of pregnancy at which transmission can occur
  • Prevention of Mother to Child Transmission of HIV
    • Scenario 1: HIV-infected pregnant women who have not received prior antiretroviral therapy
    • Scenario 2: HIV-infected women receiving antiretroviral therapy during the current pregnancy
    • Scenario 3: HIV-infected women in labour who have had no prior therapy
    • Scenario 4: Infants born to mothers who have received no antiretroviral therapy during pregnancy or intrapartum
  • Other Studies
    • Protocol 076 Study
    • Thai Study
    • The Swiss Study
    • HIV NET 012 Study
  • Choice of regimen for prevention of MTCT


Factors that influence maternal transmission

  • High maternal viral load
  • Decreased CD4 count
  • Advanced clinical disease
  • Primary infection
  • First-born twins
  • Obstetric factors
  • Chorioamnionitis
  • Mode of delivery — vaginal v/s caessarian section
  • More than 4 hours of ruptured membranes
  • Breast-feeding
  • Development of primary infection during pregnancy

Stages of pregnancy at which transmission can occur

  • In utero (in the womb)
  • During labour
  • During delivery
  • After birth (through breast-feeding)

Prevention of Mother to Child Transmission of HIV Use of antiretroviral therapy after first trimester (3 months) of pregnancy has shown to reduce the rate of maternal transmission of HIV to newborn. Antiretroviral therapy is not recommended in the first three months of pregnancy as it may have teratogenic effects on the infant, which may lead to abnormal formation of vital organs.

Following are the treatment interventions at different clinical scenarios:

Protocol 076 regimen The Protocol 076 regimen, initiated after the first trimester, should be recommended for all pregnant women with HIV infection.

Antepartum:
Oral administration of 100 mg Zidovudine (ZDV) 5 times daily, initiated at 14-34 weeks gestation and continued throughout the pregnancy.

Intrapartum:
During labour, intravenous* (I.V.) administration of ZDV in a 1 hr initial dose of 2 mg/kg body weight, followed by a continuous infusion of 1 mg/kg body weight/hour until delivery. *Also oral administration of ZDV 300 mg 3 hourly during labour may be an alternative when I.V. ZDV is not available. Postpartum: Oral administration of ZDV syrup at 2 mg/kg body weight/dose every 6 hours to the newborn for the first 6 weeks of life, beginning at 8-12 hours after birth

  • The combination of ZDV chemoprophylaxis with additional antiretroviral drugs for treatment of HIV infection is recommended for infected women whose clinical, immunologic or virologic status reuire treatment or who have HIV RNA over 1000 copies/ml regardless of clinical or immunological status.
  • Women who are in the first trimester of pregnancy may consider delaying initiation of therapy until after 10-12 weeks of gestation
  • HIV-1 infected women receiving antiretroviral therapy in whom pregnancy is identified after the first trimester should continue therapy. ZDV should be a component of the antenatal antiretroviral treatment regimen after the first trimester whenever possible.
  • Women receiving antiretroviral therapy in whom pregnancy is recognizes during the first trimester should be counseled regarding the benefits and potential risks of antiretroviral administration during this period. If therapy is discontinued during the first trimester, all the drugs should be stopped and reintroduced simultaneously to avoid the development of drug resistance.
  • Regardless of the antepartum antiretroviral regimen, ZDV administration is recommended during the intrapartum period and for the new born.
Options include:
  • Single dose Nevirapine at the onset of labour followed by a single dose of Nevirapine for the newborn at age 48 hours.
    Maternal intrapartum dose

    Single 200 mg oral dose at onset of labour

    Infant postpartum dose

    Single 2 mg/kg oral dose at age 48-72 hours*

    *If the mother received Nevirapine less than one hour prior to delivery, the infant should be given 2 mg/kg oral Nevirapine as soon as possible after birth and again at 48-72 hours.

  • Oral Zidovudine (ZDV) and Lamivudine (3TC) during labour followed by one week of oral ZDV/3TC for the newborn
    Maternal intrapartum dose

    ZDV 600 mg orally at onset of labour, followed by 300 mg orally every 3 hours until delivery and 3TC 150 mg orally at onset of labour, followed by 150 mg orally every 12 hours until delivery.

    Infant postpartum dose

    ZDV 4 mg/kg orally every 12 hours and 3TC 2 mg/kg orally every 12 hours for seven days.

  • In the immediate postpartum period, the women should have appropriate assessments (CD4 count and HIV-1 RNA copy number) to determine whether antiretroviral therapy is required for her own health.
  • The six week neonatal ZDV component of the protocol 076 regimen should be discussed with the mother and offered to the new born.
  • ZDV should be initiated as soon as possible after delivery — preferably within 6-12 hours of birth.
  • The infant should undergo early diagnosis testing so that if HIV-infected, treatment can be initiated as soon as possible.
  • In the immediate postpartum period, the women should undergo appropriate assessments (CD4 count and HIV-1 RNA copy number) to determine if antiretroviral therapy is re
  • uired for her own health.

Other Studies

Protocol 076 Study
The Protocol 076 study was a landmark study. In this, zidovudine was administered as per the regimen explained under Scenario 1 to HIV-infected pregnant women (14 to 34 weeks of gestation) with CD4 counts > 200 cells/ml. Breast-feeding was not allowed. Overall, long-course of Zidovudine significantly reduced the percentage of infants infected with HIV compared with placebo (7.9% v/s 27.7%). This corresponds to a relative risk reduction of maternal HIV transmission of 71.5% with zidovudine compared with placebo.

Thai Study
This study investigated the safety and efficacy of short-course oral zidovudine administered during late pregnancy and labour. 423 HIV-1 positive pregnant women at 34 weeks gestation were enrolled in Bangkok. Oral zidovudine 300 mg was taken twice daily beginning at 36 weeks gestation and every 3 hours from onset of labour until delivery. No zidovudine was given to the newborn. Mothers did not breast-feed. The estimated transmission risks were 9.4% on zidovudine and 18.9% on placebo. This trial showed that, in the absence of breast-feeding and with good adherence, short-course oral zidovudine can lower transmission risk by about 50%

The Swiss Study
The aim of this study was to investigate the combined effect of elective caesarian section and zidovudine prophylaxis on vertical transmission. In this study, 494 pregnant women known to be HIV-infected at delivery were enrolled in a prospective study in Switzerland between 1986- 1 July,1996.

Results:

Intervention Transmission Rate
Combined use of C-section and ZDV 0% (0 out of 31)
Elective C-section without ZDV 8% (7 out of 86)
ZDV alone 17% (4 out of 24)
No intervention 20% (55 out of 271)

The HIV NET 012 Study
This study was conducted in Uganda. Women at more than 36 weeks gestation were given either Nevirapine or Zidovudine as mentioned in Scenario 3. Women were allowed to breast-feed.

HIV transmission rates were as follows:

TimeNevirapine Zidovudine
At birth 8.1 % 10.3 %
At 6-8 weeks 11.8 % 20 %
At 14-16 weeks 13.6 % 22.1 %

This study concluded that Nevirapine lowered the risk of HIV-1 transmission by almost 50% in a breast-feeding population. This simple and relatively inexpensive regimen could decrease maternal transmission in developing countries.

Choice of regimen for prevention of MTCT
The choice of regimen for a particular patient is decided after taking into factors such as:

  • When did the mother first come for an antenatal checkup e.g. during the first trimester or did she directly come in labour?
  • Affordability
  • Compliance